Skip to main content
SpringerLink
Log in

Overview of Mechanisms Underlying Neuroimmune Diseases

  • Chapter
  • First Online:
Neuroimmune Diseases

Part of the book series: Contemporary Clinical Neuroscience ((CCNE))

Abstract

The neuroimmune diseases are caused by autoimmune demyelination, opportunistic and neurotrophic infections, paraneoplastic conditions, neurodegeneration, and neuropsychiatric disorders. These diseases are multifactorial, complex, and heterogeneous with varied clinical and pathological features and often triggered by the interplay of genetics, environmental factors, and dysregulated immune activation. The molecular mimicry of neuronal antigens, generation of onconeural antigens, inflammation-induced neuronal antigen release, and cross-presentation are thought to activate the autoreactive T and B lymphocytes. The activation of several innate immune pathways, generation of effector T cells, production of autoantibodies, inflamed blood-brain barrier, and activated microglia, astrocytes, oligodendrocytes, and neurons are known to contribute to the development of neuronal diseases. The majority of current research is focused on the genetic association, biomarker discovery, differential diagnosis, treatment choices, and identification of immunological and neurological basis of neuroimmune diseases. In this chapter, we discuss the clinical and pathological features of neuroimmune diseases and also present an overview of the current understanding of the immunological and neurological mechanisms. We also highlighted the cellular and molecular interactions in the generation of autoantibodies, inflammatory CD4+ and CD8+ T cells, reactive microglia and astrocytes, and importance of the blood-brain barrier in neuroinflammation and autoimmunity.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 229.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 299.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 299.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Abbreviations

AChR:

acetylcholine receptor

AD:

Alzheimer’s disease

ADEM:

acute disseminated encephalomyelitis

ALS:

amyotrophic lateral sclerosis

AMPA:

α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid

ANNA-1:

anti-neuronal nuclear antibody type 1

AQP4:

aquaporin 4

ASD:

autism spectrum disorder

BBB:

blood-brain barrier

BCSFB:

blood-cerebrospinal fluid barrier

BNB:

blood-nerve barrier

Bregs:

regulatory B cells

Caspr2:

anti-contactin-associated protein 2

CNS:

central nervous system

CSF:

cerebrospinal fluid

DAMPs:

damage-associated molecular patterns

EAE:

experimental autoimmune encephalomyelitis

GABA:

gamma-aminobutyric acid

GAD65:

glutamic acid decarboxylase 65

HD:

Huntington’s disease

HSV:

herpes simplex virus

HTT:

huntingtin

LGI1:

leucine-rich glioma-inactivated-1

MAG:

myelin-associated glycoprotein

MBP:

myelin basic protein

mGluR:

metabotropic glutamate receptor

MOG:

myelin oligodendrocyte glycoprotein

MRI:

magnetic resonance imaging

MS:

multiple sclerosis

NMDA:

anti-N-methyl-D-aspartate

NMOSD:

neuromyelitis optica spectrum disorders

PCA2:

Purkinje cell cytoplasmic antibody 2

PD:

Parkinson’s disease

PML:

progressive multifocal leukoencephalopathy

PP-MS:

primary progressive multiple sclerosis

RR-MS:

relapsing-remitting multiple sclerosis

SCLC:

small-cell lung carcinoma

SLE:

systemic lupus erythematosus

SOD1:

superoxide dismutase 1

SP-MS:

secondary progressive multiple sclerosis

SPS:

stiff-person syndrome

Tregs:

regulatory CD4+ T cells

TREM2:

triggering receptor expressed on myeloid cells 2

Trm:

tissue-resident memory T cells

VZV:

varicella-zoster virus

WNV:

West Nile virus

References

  1. Ransohoff RM, Schafer D, Vincent A, Blachere NE, Bar-Or A. Neuroinflammation: ways in which the immune system affects the brain. Neurotherapeutics. 2015;12(4):896–909. https://doi.org/10.1007/s13311-015-0385-3. Epub 2015/08/27. PubMed PMID: 26306439; PubMed Central PMCID: PMCPMC4604183.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  2. Golumbek P. Pharmacologic agents for pediatric neuroimmune disorders. Semin Pediatr Neurol. 2010;17(4):245–53. https://doi.org/10.1016/j.spen.2010.10.007. Epub 2010/12/25. PubMed PMID: 21183131.

    Article  PubMed  Google Scholar 

  3. Reinhold AK, Rittner HL. Barrier function in the peripheral and central nervous system-a review. Pflugers Arch. 2017;469(1):123–34. https://doi.org/10.1007/s00424-016-1920-8. Epub 2016/12/14. PubMed PMID: 27957611.

    Article  CAS  PubMed  Google Scholar 

  4. Sonar SA, Lal G. Blood-brain barrier and its function during inflammation and autoimmunity. J Leukoc Biol. 2018;103(5):839–53. https://doi.org/10.1002/JLB.1RU1117-428R. Epub 2018/02/13. PubMed PMID: 29431873.

    Article  CAS  PubMed  Google Scholar 

  5. Johanson CE, Stopa EG, McMillan PN. The blood-cerebrospinal fluid barrier: structure and functional significance. Methods Mol Biol. 2011;686:101–31. https://doi.org/10.1007/978-1-60761-938-3_4. Epub 2010/11/18. PubMed PMID: 21082368.

    Article  CAS  PubMed  Google Scholar 

  6. Balusu S, Brkic M, Libert C, Vandenbroucke RE. The choroid plexus-cerebrospinal fluid interface in Alzheimer’s disease: more than just a barrier. Neural Regen Res. 2016;11(4):534–7. https://doi.org/10.4103/1673-5374.180372. Epub 2016/05/24. PubMed PMID: 27212900; PubMed Central PMCID: PMCPMC4870896.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  7. Weise G, Stoll G. Magnetic resonance imaging of blood brain/nerve barrier dysfunction and leukocyte infiltration: closely related or discordant? Front Neurol. 2012;3:178. https://doi.org/10.3389/fneur.2012.00178. Epub 2012/12/26. PubMed PMID: 23267343; PubMed Central PMCID: PMCPMC3527731.

    Article  PubMed Central  PubMed  Google Scholar 

  8. Taipa R, Ferreira V, Brochado P, Robinson A, Reis I, Marques F, et al. Inflammatory pathology markers (activated microglia and reactive astrocytes) in early and late onset Alzheimer disease: a post mortem study. Neuropathol Appl Neurobiol. 2018;44(3):298–313. https://doi.org/10.1111/nan.12445. Epub 2017/10/19. PubMed PMID: 29044639.

    Article  CAS  PubMed  Google Scholar 

  9. Hughes RA, Mehndiratta MM, Rajabally YA. Corticosteroids for chronic inflammatory demyelinating polyradiculoneuropathy. Cochrane Database Syst Rev. 2017;(11):CD002062. https://doi.org/10.1002/14651858.CD002062.pub4. Epub 2017/12/01. PubMed PMID: 29185258.

  10. Lorscheider J, Benkert P, Lienert C, Hanni P, Derfuss T, Kuhle J, et al. Comparative analysis of natalizumab versus fingolimod as second-line treatment in relapsing-remitting multiple sclerosis. Mult Scler. 2018;24(6):777–85. https://doi.org/10.1177/1352458518768433. Epub 2018/04/25. PubMed PMID: 29685071.

    Article  CAS  PubMed  Google Scholar 

  11. Faissner S, Gold R. Efficacy and safety of the newer multiple sclerosis drugs approved since 2010. CNS Drugs. 2018;32(3):269–87. https://doi.org/10.1007/s40263-018-0488-6. Epub 2018/03/31. PubMed PMID: 29600441.

    Article  CAS  PubMed  Google Scholar 

  12. Pihl-Jensen G, Frederiksen JL. 25-Hydroxyvitamin D levels in acute monosymptomatic optic neuritis: relation to clinical severity, paraclinical findings and risk of multiple sclerosis. J Neurol. 2015;262(7):1646–54. https://doi.org/10.1007/s00415-015-7740-5. Epub 2015/05/02. PubMed PMID: 25929657.

    Article  CAS  PubMed  Google Scholar 

  13. Titulaer MJ, Hoftberger R, Iizuka T, Leypoldt F, McCracken L, Cellucci T, et al. Overlapping demyelinating syndromes and anti-N-methyl-D-aspartate receptor encephalitis. Ann Neurol. 2014;75(3):411–28. https://doi.org/10.1002/ana.24117. Epub 2014/04/05. PubMed PMID: 24700511; PubMed Central PMCID: PMCPMC4016175.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  14. Luo JJ, Lv H, Sun W, Zhao J, Hao HJ, Gao F, et al. Anti-N-methyl-d-aspartate receptor encephalitis in a patient with neuromyelitis optica spectrum disorders. Mult Scler Relat Disord. 2016;8:74–7. https://doi.org/10.1016/j.msard.2016.05.002. Epub 2016/07/28. PubMed PMID: 27456878.

    Article  PubMed  Google Scholar 

  15. Kamm C, Zettl UK. Autoimmune disorders affecting both the central and peripheral nervous system. Autoimmun Rev. 2012;11(3):196–202. https://doi.org/10.1016/j.autrev.2011.05.012. Epub 2011/05/31. PubMed PMID: 21619947.

    Article  CAS  PubMed  Google Scholar 

  16. Lublin FD, Reingold SC, Cohen JA, Cutter GR, Sorensen PS, Thompson AJ, et al. Defining the clinical course of multiple sclerosis: the 2013 revisions. Neurology. 2014;83(3):278–86. https://doi.org/10.1212/WNL.0000000000000560. Epub 2014/05/30. PubMed PMID: 24871874; PubMed Central PMCID: PMCPMC4117366.

    Article  PubMed Central  PubMed  Google Scholar 

  17. Miller E. Multiple sclerosis. Adv Exp Med Biol. 2012;724:222–38. https://doi.org/10.1007/978-1-4614-0653-2_17. Epub 2012/03/14. PubMed PMID: 22411246.

    Article  CAS  PubMed  Google Scholar 

  18. Hardy TA, Reddel SW, Barnett MH, Palace J, Lucchinetti CF, Weinshenker BG. Atypical inflammatory demyelinating syndromes of the CNS. Lancet Neurol. 2016;15(9):967–81. https://doi.org/10.1016/S1474-4422(16)30043-6. Epub 2016/08/02. PubMed PMID: 27478954.

    Article  CAS  PubMed  Google Scholar 

  19. Kurdi M, Ramsay D. Balo’s concentric lesions with concurrent features of Schilder’s disease in relapsing multiple sclerosis: neuropathological findings. Autops Case Rep. 2016;6(4):21–6. https://doi.org/10.4322/acr.2016.058. Epub 2017/02/18. PubMed PMID: 28210570; PubMed Central PMCID: PMCPMC5304558.

    Article  PubMed Central  PubMed  Google Scholar 

  20. Rotem RS, Chodick G, Davidovitch M, Hauser R, Coull BA, Weisskopf MG. Congenital abnormalities of the male reproductive system and risk of autism spectrum disorders. Am J Epidemiol. 2018;187(4):656–63. https://doi.org/10.1093/aje/kwx367. Epub 2018/02/17. PubMed PMID: 29452340; PubMed Central PMCID: PMCPMC5888926.

    Article  PubMed Central  PubMed  Google Scholar 

  21. Schieve LA, Shapira SK. Invited commentary: male reproductive system congenital malformations and the risk of autism spectrum disorder. Am J Epidemiol. 2018;187(4):664–7. https://doi.org/10.1093/aje/kwx369. Epub 2018/02/17. PubMed PMID: 29452336; PubMed Central PMCID: PMCPMC5884740.

    Article  PubMed  Google Scholar 

  22. Sinmaz N, Nguyen T, Tea F, Dale RC, Brilot F. Mapping autoantigen epitopes: molecular insights into autoantibody-associated disorders of the nervous system. J Neuroinflammation. 2016;13(1):219. https://doi.org/10.1186/s12974-016-0678-4. Epub 2016/09/01. PubMed PMID: 27577085; PubMed Central PMCID: PMCPMC5006540.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  23. Zuliani L, Zoccarato M, Gastaldi M, Iorio R, Evoli A, Biagioli T, et al. Diagnostics of autoimmune encephalitis associated with antibodies against neuronal surface antigens. Neurol Sci. 2017;38(Suppl 2):225–9. https://doi.org/10.1007/s10072-017-3032-4. Epub 2017/10/17. PubMed PMID: 29030767.

    Article  PubMed  Google Scholar 

  24. Dalmau J, Graus F. Antibody-mediated encephalitis. N Engl J Med. 2018;378(9):840–51. https://doi.org/10.1056/NEJMra1708712. Epub 2018/03/01. PubMed PMID: 29490181.

    Article  PubMed  Google Scholar 

  25. Lai M, Huijbers MG, Lancaster E, Graus F, Bataller L, Balice-Gordon R, et al. Investigation of LGI1 as the antigen in limbic encephalitis previously attributed to potassium channels: a case series. Lancet Neurol. 2010;9(8):776–85. https://doi.org/10.1016/S1474-4422(10)70137-X. Epub 2010/06/29. PubMed PMID: 20580615; PubMed Central PMCID: PMCPMC3086669.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  26. Okumura A, Nakazawa M, Igarashi A, Abe S, Ikeno M, Nakahara E, et al. Anti-aquaporin 4 antibody-positive acute disseminated encephalomyelitis. Brain Dev. 2015;37(3):339–43. https://doi.org/10.1016/j.braindev.2014.04.013. Epub 2014/05/20. PubMed PMID: 24837901.

    Article  PubMed  Google Scholar 

  27. Tanaka M, Tanaka K. Anti-MOG antibodies in adult patients with demyelinating disorders of the central nervous system. J Neuroimmunol. 2014;270(1–2):98–9. https://doi.org/10.1016/j.jneuroim.2014.03.001. Epub 2014/04/08. PubMed PMID: 24703097.

    Article  CAS  PubMed  Google Scholar 

  28. Weissert R. Adaptive immunity is the key to the understanding of autoimmune and paraneoplastic inflammatory central nervous system disorders. Front Immunol. 2017;8:336. https://doi.org/10.3389/fimmu.2017.00336. Epub 2017/04/08. PubMed PMID: 28386263; PubMed Central PMCID: PMCPMC5362596.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  29. Tekgul H, Polat M, Kitis O, Serdaroglu G, Tosun A, Terlemez S, et al. T-cell subsets and interleukin-6 response in Rasmussen’s encephalitis. Pediatr Neurol. 2005;33(1):39–45. https://doi.org/10.1016/j.pediatrneurol.2005.01.007. Epub 2005/05/07. PubMed PMID: 15876522.

    Article  PubMed  Google Scholar 

  30. Bien CG, Vincent A, Barnett MH, Becker AJ, Blumcke I, Graus F, et al. Immunopathology of autoantibody-associated encephalitides: clues for pathogenesis. Brain J Neurol. 2012;135(Pt 5):1622–38. https://doi.org/10.1093/brain/aws082. Epub 2012/04/28. PubMed PMID: 22539258.

    Article  Google Scholar 

  31. Shimizu F, Kanda T. Disruption of the blood-brain barrier in inflammatory neurological diseases. Brain Nerve. 2013;65(2):165–76. Epub 2013/02/13. PubMed PMID: 23399674.

    CAS  PubMed  Google Scholar 

  32. Chen HA, Lin YJ, Chen PC, Chen TY, Lin KC, Cheng HH. Systemic lupus erythematosus complicated with posterior reversible encephalopathy syndrome and intracranial vasculopathy. Int J Rheum Dis. 2010;13(4):e79–82. https://doi.org/10.1111/j.1756-185X.2010.01545.x. Epub 2011/01/05. PubMed PMID: 21199460.

    Article  PubMed  Google Scholar 

  33. Kakati S, Barman B, Ahmed SU, Hussain M. Neurological manifestations in systemic lupus erythematosus: a single Centre Study from North East India. J Clin Diagn Res. 2017;11(1):OC05–OC9. https://doi.org/10.7860/JCDR/2017/23773.9280. Epub 2017/03/10. PubMed PMID: 28273990; PubMed Central PMCID: PMCPMC5324435.

    Article  PubMed Central  PubMed  Google Scholar 

  34. Ozkul A, Yilmaz A, Akyol A, Kiylioglu N. Cerebral vasculitis as a major manifestation of rheumatoid arthritis. Acta Clin Belg. 2015;70(5):359–63. https://doi.org/10.1080/17843286.2015.1131965. Epub 2016/01/09. PubMed PMID: 26743575.

    Article  CAS  PubMed  Google Scholar 

  35. Bhattacharyya S, Helfgott SM. Neurologic complications of systemic lupus erythematosus, sjogren syndrome, and rheumatoid arthritis. Semin Neurol. 2014;34(4):425–36. https://doi.org/10.1055/s-0034-1390391. Epub 2014/11/05. PubMed PMID: 25369438.

    Article  PubMed  Google Scholar 

  36. Lvovich S, Goldsmith DP. Neurological complications of rheumatic disease. Semin Pediatr Neurol. 2017;24(1):54–9. https://doi.org/10.1016/j.spen.2016.12.007. Epub 2017/08/07. PubMed PMID: 28779866.

    Article  PubMed  Google Scholar 

  37. Zandman-Goddard G, Chapman J, Shoenfeld Y. Autoantibodies involved in neuropsychiatric SLE and antiphospholipid syndrome. Semin Arthritis Rheum. 2007;36(5):297–315. https://doi.org/10.1016/j.semarthrit.2006.11.003. Epub 2007/01/30. PubMed PMID: 17258299.

    Article  CAS  PubMed  Google Scholar 

  38. Scarborough M, Thwaites GE. The diagnosis and management of acute bacterial meningitis in resource-poor settings. Lancet Neurol. 2008;7(7):637–48. https://doi.org/10.1016/S1474-4422(08)70139-X. Epub 2008/06/21. PubMed PMID: 18565457.

    Article  PubMed  Google Scholar 

  39. Oordt-Speets AM, Bolijn R, van Hoorn RC, Bhavsar A, Kyaw MH. Global etiology of bacterial meningitis: a systematic review and meta-analysis. PLoS One. 2018;13(6):e0198772. https://doi.org/10.1371/journal.pone.0198772. Epub 2018/06/12. PubMed PMID: 29889859; PubMed Central PMCID: PMCPMC5995389 performed under contract by Pallas Health Research and Consultancy, Rotterdam, The Netherlands. AMO, RB, and RCH are employees of Pallas Health Research and Consultancy, Rotterdam, The Netherlands. AB and MHK are employees of Sanofi-Pasteur. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  40. McGill F, Griffiths MJ, Solomon T. Viral meningitis: current issues in diagnosis and treatment. Curr Opin Infect Dis. 2017;30(2):248–56. https://doi.org/10.1097/QCO.0000000000000355. Epub 2017/01/25. PubMed PMID: 28118219.

    Article  PubMed  Google Scholar 

  41. Hakyemez IN, Erdem H, Beraud G, Lurdes M, Silva-Pinto A, Alexandru C, et al. Prediction of unfavorable outcomes in cryptococcal meningitis: results of the multicenter Infectious Diseases International Research Initiative (ID-IRI) cryptococcal meningitis study. Eur J Clin Microbiol Infect Dis. 2018;37(7):1231–40. https://doi.org/10.1007/s10096-017-3142-1. Epub 2017/12/09. PubMed PMID: 29218468.

    Article  CAS  PubMed  Google Scholar 

  42. Singh TD, Fugate JE, Hocker S, Wijdicks EFM, Aksamit AJ Jr, Rabinstein AA. Predictors of outcome in HSV encephalitis. J Neurol. 2016;263(2):277–89. https://doi.org/10.1007/s00415-015-7960-8. Epub 2015/11/17. PubMed PMID: 26568560.

    Article  CAS  PubMed  Google Scholar 

  43. Anukumar B, Sapkal GN, Tandale BV, Balasubramanian R, West GD. Nile encephalitis outbreak in Kerala, India, 2011. J Clin Virol. 2014;61(1):152–5. https://doi.org/10.1016/j.jcv.2014.06.003. Epub 2014/07/06. PubMed PMID: 24985196.

    Article  CAS  PubMed  Google Scholar 

  44. Rudolf I, Betasova L, Blazejova H, Venclikova K, Strakova P, Sebesta O, et al. West Nile virus in overwintering mosquitoes, Central Europe. Parasit Vectors. 2017;10(1):452. https://doi.org/10.1186/s13071-017-2399-7. Epub 2017/10/04. PubMed PMID: 28969685; PubMed Central PMCID: PMCPMC5625652.

    Article  PubMed Central  PubMed  Google Scholar 

  45. Chin RL, Sander HW, Brannagan TH 3rd, De Sousa E, Latov N. Demyelinating neuropathy in patients with hepatitis C virus infection. J Clin Neuromuscul Dis. 2010;11(4):209–12. https://doi.org/10.1097/CND.0b013e3181b701c1. Epub 2010/06/03. PubMed PMID: 20516810.

    Article  PubMed  Google Scholar 

  46. Cleto TL, de Araujo LF, Capuano KG, Rego Ramos A, Prata-Barbosa A. Peripheral neuropathy associated with Zika virus infection. Pediatr Neurol. 2016;65:e1–2. https://doi.org/10.1016/j.pediatrneurol.2016.08.011. Epub 2016/10/13. PubMed PMID: 27729183.

    Article  PubMed  Google Scholar 

  47. Conliffe TD, Dholakia M, Broyer Z. Herpes zoster radiculopathy treated with fluoroscopically-guided selective nerve root injection. Pain Physician. 2009;12(5):851–3. Epub 2009/09/30. PubMed PMID: 19787010.

    Article  PubMed  Google Scholar 

  48. Tuerlinckx D, Bodart E, Jamart J, Glupczynski Y. Prediction of Lyme meningitis based on a logistic regression model using clinical and cerebrospinal fluid analysis: a European study. Pediatr Infect Dis J. 2009;28(5):394–7. https://doi.org/10.1097/INF.0b013e318191f035. Epub 2009/03/20. PubMed PMID: 19295463.

    Article  PubMed  Google Scholar 

  49. Llewellyn GN, Alvarez-Carbonell D, Chateau M, Karn J, Cannon PM. HIV-1 infection of microglial cells in a reconstituted humanized mouse model and identification of compounds that selectively reverse HIV latency. J Neurovirol. 2018;24(2):192–203. https://doi.org/10.1007/s13365-017-0604-2. Epub 2017/12/20. PubMed PMID: 29256041; PubMed Central PMCID: PMCPMC5910454.

    Article  CAS  PubMed  Google Scholar 

  50. Gray LR, Turville SG, Hitchen TL, Cheng WJ, Ellett AM, Salimi H, et al. HIV-1 entry and trans-infection of astrocytes involves CD81 vesicles. PLoS One. 2014;9(2):e90620. https://doi.org/10.1371/journal.pone.0090620. Epub 2014/03/04. PubMed PMID: 24587404; PubMed Central PMCID: PMCPMC3938779.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  51. Nookala AR, Mitra J, Chaudhari NS, Hegde ML, Kumar A. An overview of human immunodeficiency virus type 1-associated common neurological complications: does aging pose a challenge? J Alzheimers Dis. 2017;60(s1):S169–S93. https://doi.org/10.3233/JAD-170473. Epub 2017/08/12. PubMed PMID: 28800335; PubMed Central PMCID: PMCPMC6152920.

    Article  PubMed Central  PubMed  Google Scholar 

  52. Cinque P, Koralnik IJ, Gerevini S, Miro JM, Price RW. Progressive multifocal leukoencephalopathy in HIV-1 infection. Lancet Infect Dis. 2009;9(10):625–36. https://doi.org/10.1016/S1473-3099(09)70226-9. Epub 2009/09/26. PubMed PMID: 19778765; PubMed Central PMCID: PMCPMC2919371.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  53. Mamidi A, DeSimone JA, Pomerantz RJ. Central nervous system infections in individuals with HIV-1 infection. J Neurovirol. 2002;8(3):158–67. https://doi.org/10.1080/13550280290049723. Epub 2002/06/08. PubMed PMID: 12053271.

    Article  PubMed  Google Scholar 

  54. Brahic M, Bureau JF, Michiels T. The genetics of the persistent infection and demyelinating disease caused by Theiler’s virus. Annu Rev Microbiol. 2005;59:279–98. https://doi.org/10.1146/annurev.micro.59.030804.121242. Epub 2005/09/13. PubMed PMID: 16153171.

    Article  CAS  PubMed  Google Scholar 

  55. Wucherpfennig KW, Strominger JL. Molecular mimicry in T cell-mediated autoimmunity: viral peptides activate human T cell clones specific for myelin basic protein. Cell. 1995;80(5):695–705. Epub 1995/03/10. PubMed PMID: 7534214.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Fujinami RS, Oldstone MB. Amino acid homology between the encephalitogenic site of myelin basic protein and virus: mechanism for autoimmunity. Science. 1985;230(4729):1043–5. Epub 1985/11/29. PubMed PMID: 2414848.

    Article  CAS  PubMed  Google Scholar 

  57. Zheng MM, Zhang XH. Cross-reactivity between human cytomegalovirus peptide 981-1003 and myelin oligodendroglia glycoprotein peptide 35-55 in experimental autoimmune encephalomyelitis in Lewis rats. Biochem Biophys Res Commun. 2014;443(3):1118–23. https://doi.org/10.1016/j.bbrc.2013.12.122. Epub 2014/01/07. PubMed PMID: 24388990.

    Article  CAS  PubMed  Google Scholar 

  58. Varrin-Doyer M, Spencer CM, Schulze-Topphoff U, Nelson PA, Stroud RM, Cree BA, et al. Aquaporin 4-specific T cells in neuromyelitis optica exhibit a Th17 bias and recognize Clostridium ABC transporter. Ann Neurol. 2012;72(1):53–64. https://doi.org/10.1002/ana.23651. Epub 2012/07/19. PubMed PMID: 22807325; PubMed Central PMCID: PMCPMC3405197.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  59. Rodriguez Y, Rojas M, Pacheco Y, Acosta-Ampudia Y, Ramirez-Santana C, Monsalve DM, et al. Guillain-Barre syndrome, transverse myelitis and infectious diseases. Cell Mol Immunol. 2018;15(6):547–62. https://doi.org/10.1038/cmi.2017.142. Epub 2018/01/30. PubMed PMID: 29375121; PubMed Central PMCID: PMCPMC6079071.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  60. Gebauer C, Pignolet B, Yshii L, Maure E, Bauer J, Liblau R. CD4+ and CD8+ T cells are both needed to induce paraneoplastic neurological disease in a mouse model. Oncoimmunology. 2017;6(2):e1260212. Epub 2017/03/28. doi: 10.1080/2162402X.2016.1260212. PubMed PMID: 28344867; PubMed Central PMCID: PMCPMC5353919.

    Article  PubMed  Google Scholar 

  61. Sepulveda M, Sola-Valls N, Escudero D, Rojc B, Baron M, Hernandez-Echebarria L, et al. Clinical profile of patients with paraneoplastic neuromyelitis optica spectrum disorder and aquaporin-4 antibodies. Mult Scler. 2018;24(13):1753–9. https://doi.org/10.1177/1352458517731914. Epub 2017/09/19. PubMed PMID: 28920766; PubMed Central PMCID: PMCPMC5832634.

    Article  CAS  PubMed  Google Scholar 

  62. Lucchinetti CF, Kimmel DW, Lennon VA. Paraneoplastic and oncologic profiles of patients seropositive for type 1 antineuronal nuclear autoantibodies. Neurology. 1998;50(3):652–7. Epub 1998/04/01. PubMed PMID: 9521251.

    Article  CAS  PubMed  Google Scholar 

  63. Pittock SJ, Lucchinetti CF, Lennon VA. Anti-neuronal nuclear autoantibody type 2: paraneoplastic accompaniments. Ann Neurol. 2003;53(5):580–7. https://doi.org/10.1002/ana.10518. Epub 2003/05/06. PubMed PMID: 12730991.

    Article  CAS  PubMed  Google Scholar 

  64. Melzer N, Meuth SG, Wiendl H. Paraneoplastic and non-paraneoplastic autoimmunity to neurons in the central nervous system. J Neurol. 2013;260(5):1215–33. https://doi.org/10.1007/s00415-012-6657-5. Epub 2012/09/18. PubMed PMID: 22983427; PubMed Central PMCID: PMCPMC3642360.

    Article  CAS  PubMed  Google Scholar 

  65. Hoftberger R, Rosenfeld MR, Dalmau J. Update on neurological paraneoplastic syndromes. Curr Opin Oncol. 2015;27(6):489–95. https://doi.org/10.1097/CCO.0000000000000222. Epub 2015/09/04. PubMed PMID: 26335665; PubMed Central PMCID: PMCPMC4640358.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  66. Lancaster E, Dalmau J. Neuronal autoantigens – pathogenesis, associated disorders and antibody testing. Nat Rev Neurol. 2012;8(7):380–90. https://doi.org/10.1038/nrneurol.2012.99. Epub 2012/06/20. PubMed PMID: 22710628; PubMed Central PMCID: PMCPMC3718498.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  67. Boronat A, Sabater L, Saiz A, Dalmau J, Graus F. GABA(B) receptor antibodies in limbic encephalitis and anti-GAD-associated neurologic disorders. Neurology. 2011;76(9):795–800. https://doi.org/10.1212/WNL.0b013e31820e7b8d. Epub 2011/03/02. PubMed PMID: 21357831; PubMed Central PMCID: PMCPMC3053332.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  68. Kuter K, Olech L, Glowacka U. Prolonged dysfunction of astrocytes and activation of microglia accelerate degeneration of dopaminergic neurons in the rat substantia Nigra and block compensation of early motor dysfunction induced by 6-OHDA. Mol Neurobiol. 2018;55(4):3049–66. https://doi.org/10.1007/s12035-017-0529-z. Epub 2017/05/04. PubMed PMID: 28466266; PubMed Central PMCID: PMCPMC5842510.

    Article  CAS  PubMed  Google Scholar 

  69. Wang L, Popko B, Roos RP. An enhanced integrated stress response ameliorates mutant SOD1-induced ALS. Hum Mol Genet. 2014;23(10):2629–38. https://doi.org/10.1093/hmg/ddt658. Epub 2013/12/26. PubMed PMID: 24368417; PubMed Central PMCID: PMCPMC3990163.

    Article  CAS  PubMed  Google Scholar 

  70. Kruger R, Kuhn W, Muller T, Woitalla D, Graeber M, Kosel S, et al. Ala30Pro mutation in the gene encoding alpha-synuclein in Parkinson’s disease. Nat Genet. 1998;18(2):106–8. https://doi.org/10.1038/ng0298-106. Epub 1998/02/14. PubMed PMID: 9462735.

    Article  CAS  PubMed  Google Scholar 

  71. Jay TR, von Saucken VE, Landreth GE. TREM2 in neurodegenerative diseases. Mol Neurodegener. 2017;12(1):56. https://doi.org/10.1186/s13024-017-0197-5. Epub 2017/08/05. PubMed PMID: 28768545; PubMed Central PMCID: PMCPMC5541421.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  72. Morris G, Stubbs B, Kohler CA, Walder K, Slyepchenko A, Berk M, et al. The putative role of oxidative stress and inflammation in the pathophysiology of sleep dysfunction across neuropsychiatric disorders: focus on chronic fatigue syndrome, bipolar disorder and multiple sclerosis. Sleep Med Rev. 2018;41:255–65. https://doi.org/10.1016/j.smrv.2018.03.007. Epub 2018/05/16. PubMed PMID: 29759891.

    Article  PubMed  Google Scholar 

  73. Bhattacharya A, Derecki NC, Lovenberg TW, Drevets WC. Role of neuro-immunological factors in the pathophysiology of mood disorders. Psychopharmacology. 2016;233(9):1623–36. https://doi.org/10.1007/s00213-016-4214-0. Epub 2016/01/25. PubMed PMID: 26803500.

    Article  CAS  PubMed  Google Scholar 

  74. Jones KA, Thomsen C. The role of the innate immune system in psychiatric disorders. Mol Cell Neurosci. 2013;53:52–62. https://doi.org/10.1016/j.mcn.2012.10.002. Epub 2012/10/16. PubMed PMID: 23064447.

    Article  CAS  PubMed  Google Scholar 

  75. Dvir Y, Ford JD, Hill M, Frazier JA. Childhood maltreatment, emotional dysregulation, and psychiatric comorbidities. Harv Rev Psychiatry. 2014;22(3):149–61. https://doi.org/10.1097/HRP.0000000000000014. Epub 2014/04/08. PubMed PMID: 24704784; PubMed Central PMCID: PMCPMC4091823.

    Article  PubMed Central  PubMed  Google Scholar 

  76. Bland P. Depression in adults linked to maltreatment in childhood. Practitioner. 2017;261(1802):7. Epub 2017/11/16. PubMed PMID: 29139275.

    PubMed  Google Scholar 

  77. Aaltonen KI, Rosenstrom T, Baryshnikov I, Karpov B, Melartin T, Suominen K, et al. Mediating role of borderline personality disorder traits in the effects of childhood maltreatment on suicidal behaviour among mood disorder patients. Eur Psychiatry. 2017;44:53–60. https://doi.org/10.1016/j.eurpsy.2017.03.011. Epub 2017/05/26. PubMed PMID: 28545009.

    Article  CAS  PubMed  Google Scholar 

  78. Jeltsch-David H, Muller S. Autoimmunity, neuroinflammation, pathogen load: a decisive crosstalk in neuropsychiatric SLE. J Autoimmun. 2016;74:13–26. https://doi.org/10.1016/j.jaut.2016.04.005. Epub 2016/10/26. PubMed PMID: 27137989.

    Article  CAS  PubMed  Google Scholar 

  79. Chastain EM, Miller SD. Molecular mimicry as an inducing trigger for CNS autoimmune demyelinating disease. Immunol Rev. 2012;245(1):227–38. https://doi.org/10.1111/j.1600-065X.2011.01076.x. Epub 2011/12/16. PubMed PMID: 22168423; PubMed Central PMCID: PMCPMC3586283.

    Article  CAS  PubMed  Google Scholar 

  80. Wandinger K, Jabs W, Siekhaus A, Bubel S, Trillenberg P, Wagner H, et al. Association between clinical disease activity and Epstein-Barr virus reactivation in MS. Neurology. 2000;55(2):178–84. Epub 2000/07/26. PubMed PMID: 10908887.

    Article  CAS  PubMed  Google Scholar 

  81. Sonar SA, Lal G. Differentiation and transmigration of CD4 T cells in neuroinflammation and autoimmunity. Front Immunol. 2017;8:1695. https://doi.org/10.3389/fimmu.2017.01695. Epub 2017/12/15. PubMed PMID: 29238350; PubMed Central PMCID: PMCPMC5712560.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  82. Braniste V, Al-Asmakh M, Kowal C, Anuar F, Abbaspour A, Toth M, et al. The gut microbiota influences blood-brain barrier permeability in mice. Sci Transl Med. 2014;6(263):263ra158. https://doi.org/10.1126/scitranslmed.3009759. Epub 2014/11/21. PubMed PMID: 25411471; PubMed Central PMCID: PMC4396848.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  83. Saijo K, Glass CK. Microglial cell origin and phenotypes in health and disease. Nat Rev Immunol. 2011;11(11):775–87. https://doi.org/10.1038/nri3086. PubMed PMID: 22025055.

    Article  CAS  PubMed  Google Scholar 

  84. Singh S, Metz I, Amor S, van der Valk P, Stadelmann C, Bruck W. Microglial nodules in early multiple sclerosis white matter are associated with degenerating axons. Acta Neuropathol. 2013;125(4):595–608. https://doi.org/10.1007/s00401-013-1082-0. Epub 2013/01/29. PubMed PMID: 23354834; PubMed Central PMCID: PMCPMC3611040.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  85. Murphy AC, Lalor SJ, Lynch MA, Mills KH. Infiltration of Th1 and Th17 cells and activation of microglia in the CNS during the course of experimental autoimmune encephalomyelitis. Brain Behav Immun. 2010;24(4):641–51. https://doi.org/10.1016/j.bbi.2010.01.014. PubMed PMID: 20138983.

    Article  CAS  PubMed  Google Scholar 

  86. Kwong B, Rua R, Gao Y, Flickinger J Jr, Wang Y, Kruhlak MJ, et al. T-bet-dependent NKp46(+) innate lymphoid cells regulate the onset of TH17-induced neuroinflammation. Nat Immunol. 2017;18(10):1117–27. https://doi.org/10.1038/ni.3816. Epub 2017/08/15. PubMed PMID: 28805812; PubMed Central PMCID: PMCPMC5605431.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  87. Pikor NB, Astarita JL, Summers-Deluca L, Galicia G, Qu J, Ward LA, et al. Integration of Th17- and lymphotoxin-derived signals initiates meningeal-resident stromal cell remodeling to propagate neuroinflammation. Immunity. 2015;43(6):1160–73. https://doi.org/10.1016/j.immuni.2015.11.010. Epub 2015/12/20. PubMed PMID: 26682987.

    Article  CAS  PubMed  Google Scholar 

  88. Pikor NB, Prat A, Bar-Or A, Gommerman JL. Meningeal tertiary lymphoid tissues and multiple sclerosis: a gathering place for diverse types of immune cells during CNS autoimmunity. Front Immunol. 2015;6:657. https://doi.org/10.3389/fimmu.2015.00657. Epub 2016/01/23. PubMed PMID: 26793195; PubMed Central PMCID: PMCPMC4710700.

    Article  CAS  PubMed  Google Scholar 

  89. Sonar SA, Shaikh S, Joshi N, Atre AN, Lal G. IFN-gamma promotes transendothelial migration of CD4(+) T cells across the blood-brain barrier. Immunol Cell Biol. 2017;95(9):843–53. https://doi.org/10.1038/icb.2017.56. Epub 2017/07/07. PubMed PMID: 28682305.

    Article  CAS  PubMed  Google Scholar 

  90. Sonar S, Lal G. Role of tumor necrosis factor superfamily in neuroinflammation and autoimmunity. Front Immunol. 2015;6:364. https://doi.org/10.3389/fimmu.2015.00364. Epub 2015/08/11. PubMed PMID: 26257732; PubMed Central PMCID: PMC4507150.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  91. Jager A, Dardalhon V, Sobel RA, Bettelli E, Kuchroo VK. Th1, Th17, and Th9 effector cells induce experimental autoimmune encephalomyelitis with different pathological phenotypes. J Immunol. 2009;183(11):7169–77. PubMed PMID: 19890056.

    Article  PubMed  Google Scholar 

  92. Ronchi F, Basso C, Preite S, Reboldi A, Baumjohann D, Perlini L, et al. Experimental priming of encephalitogenic Th1/Th17 cells requires pertussis toxin-driven IL-1beta production by myeloid cells. Nat Commun. 2016;7:11541. https://doi.org/10.1038/ncomms11541. Epub 2016/05/18. PubMed PMID: 27189410; PubMed Central PMCID: PMC4873938.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  93. Kebir H, Ifergan I, Alvarez JI, Bernard M, Poirier J, Arbour N, et al. Preferential recruitment of interferon-gamma-expressing TH17 cells in multiple sclerosis. Ann Neurol. 2009;66(3):390–402. https://doi.org/10.1002/ana.21748. PubMed PMID: 19810097.

    Article  CAS  PubMed  Google Scholar 

  94. Abromson-Leeman S, Bronson RT, Dorf ME. Encephalitogenic T cells that stably express both T-bet and ROR gamma t consistently produce IFNgamma but have a spectrum of IL-17 profiles. J Neuroimmunol. 2009;215(1–2):10–24. https://doi.org/10.1016/j.jneuroim.2009.07.007. PubMed PMID: 19692128; PubMed Central PMCID: PMCPMC2761534.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  95. Codarri L, Gyulveszi G, Tosevski V, Hesske L, Fontana A, Magnenat L, et al. RORgammat drives production of the cytokine GM-CSF in helper T cells, which is essential for the effector phase of autoimmune neuroinflammation. Nat Immunol. 2011;12(6):560–7. https://doi.org/10.1038/ni.2027. PubMed PMID: 21516112.

    Article  CAS  PubMed  Google Scholar 

  96. Hirota K, Duarte JH, Veldhoen M, Hornsby E, Li Y, Cua DJ, et al. Fate mapping of IL-17-producing T cells in inflammatory responses. Nat Immunol. 2011;12(3):255–63. https://doi.org/10.1038/ni.1993. Epub 2011/02/01. PubMed PMID: 21278737; PubMed Central PMCID: PMC3040235.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  97. Ghoreschi K, Laurence A, Yang XP, Hirahara K, O’Shea JJ. T helper 17 cell heterogeneity and pathogenicity in autoimmune disease. Trends Immunol. 2011;32(9):395–401. https://doi.org/10.1016/j.it.2011.06.007. Epub 2011/07/26. PubMed PMID: 21782512; PubMed Central PMCID: PMC3163735.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  98. Malik S, Want MY, Awasthi A. The emerging roles of gamma-delta T cells in tissue inflammation in experimental autoimmune encephalomyelitis. Front Immunol. 2016;7:14. https://doi.org/10.3389/fimmu.2016.00014. PubMed PMID: 26858718; PubMed Central PMCID: PMCPMC4731487.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  99. Stromnes IM, Cerretti LM, Liggitt D, Harris RA, Goverman JM. Differential regulation of central nervous system autoimmunity by T(H)1 and T(H)17 cells. Nat Med. 2008;14(3):337–42. https://doi.org/10.1038/nm1715. Epub 2008/02/19. PubMed PMID: 18278054; PubMed Central PMCID: PMC2813727.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  100. Kroenke MA, Carlson TJ, Andjelkovic AV, Segal BM. IL-12- and IL-23-modulated T cells induce distinct types of EAE based on histology, CNS chemokine profile, and response to cytokine inhibition. J Exp Med. 2008;205(7):1535–41. https://doi.org/10.1084/jem.20080159. PubMed PMID: 18573909; PubMed Central PMCID: PMCPMC2442630.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  101. Korn T, Kallies A. T cell responses in the central nervous system. Nat Rev Immunol. 2017;17(3):179–94. https://doi.org/10.1038/nri.2016.144. Epub 2017/02/01. PubMed PMID: 28138136.

    Article  CAS  PubMed  Google Scholar 

  102. Kara EE, McKenzie DR, Bastow CR, Gregor CE, Fenix KA, Ogunniyi AD, et al. CCR2 defines in vivo development and homing of IL-23-driven GM-CSF-producing Th17 cells. Nat Commun. 2015;6:8644. https://doi.org/10.1038/ncomms9644. PubMed PMID: 26511769; PubMed Central PMCID: PMCPMC4639903.

    Article  CAS  PubMed  Google Scholar 

  103. Hori S, Nomura T, Sakaguchi S. Control of regulatory T cell development by the transcription factor Foxp3. Science. 2003;299(5609):1057–61. PubMed PMID: 12522256.

    Article  CAS  PubMed  Google Scholar 

  104. Fontenot JD, Gavin MA, Rudensky AY. Foxp3 programs the development and function of CD4+CD25+ regulatory T cells. Nat Immunol. 2003;4(4):330–6. PubMed PMID: 12612578.

    Article  CAS  PubMed  Google Scholar 

  105. Sethi A, Kulkarni N, Sonar S, Lal G. Role of miRNAs in CD4 T cell plasticity during inflammation and tolerance. Front Genet. 2013;4:8. https://doi.org/10.3389/fgene.2013.00008. Epub 2013/02/07. PubMed PMID: 23386861; PubMed Central PMCID: PMC3560369.

    Article  PubMed Central  PubMed  Google Scholar 

  106. Lal G, Zhang N, van der Touw W, Ding Y, Ju W, Bottinger EP, et al. Epigenetic regulation of Foxp3 expression in regulatory T cells by DNA methylation. J Immunol. 2009;182(1):259–73. PubMed PMID: 19109157.

    Article  CAS  PubMed  Google Scholar 

  107. Lal G, Yin N, Xu J, Lin M, Schroppel S, Ding Y, et al. Distinct inflammatory signals have physiologically divergent effects on epigenetic regulation of foxp3 expression and treg function. Am J Transplant. 2011;11(2):203–14. https://doi.org/10.1111/j.1600-6143.2010.03389.x. Epub 2011/01/12. PubMed PMID: 21219575.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  108. Kulkarni N, Sonar SA, Lal G. Plasticity of Th17 and Tregs and its clinical importance as therapeutic target in inflammatory bowel disease. Indian J Inflamm Res. 2018;1(1):R2.

    Article  Google Scholar 

  109. Cassan C, Piaggio E, Zappulla JP, Mars LT, Couturier N, Bucciarelli F, et al. Pertussis toxin reduces the number of splenic Foxp3+ regulatory T cells. J Immunol. 2006;177(3):1552–60. PubMed PMID: 16849462.

    Article  CAS  PubMed  Google Scholar 

  110. Chen X, Winkler-Pickett RT, Carbonetti NH, Ortaldo JR, Oppenheim JJ, Howard OM. Pertussis toxin as an adjuvant suppresses the number and function of CD4+CD25+ T regulatory cells. Eur J Immunol. 2006;36(3):671–80. PubMed PMID: 16479542.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  111. Chen X, Howard OM, Oppenheim JJ. Pertussis toxin by inducing IL-6 promotes the generation of IL-17-producing CD4 cells. J Immunol. 2007;178(10):6123–9. PubMed PMID: 17475838.

    Article  CAS  PubMed  Google Scholar 

  112. Villares R, Cadenas V, Lozano M, Almonacid L, Zaballos A, Martinez AC, et al. CCR6 regulates EAE pathogenesis by controlling regulatory CD4+ T-cell recruitment to target tissues. Eur J Immunol. 2009;39(6):1671–81. https://doi.org/10.1002/eji.200839123. PubMed PMID: 19499521.

    Article  CAS  PubMed  Google Scholar 

  113. Peelen E, Damoiseaux J, Smolders J, Knippenberg S, Menheere P, Tervaert JW, et al. Th17 expansion in MS patients is counterbalanced by an expanded CD39+ regulatory T cell population during remission but not during relapse. J Neuroimmunol. 2011;240–241:97–103. https://doi.org/10.1016/j.jneuroim.2011.09.013. Epub 2011/11/01. PubMed PMID: 22035960.

    Article  CAS  PubMed  Google Scholar 

  114. Viglietta V, Baecher-Allan C, Weiner HL, Hafler DA. Loss of functional suppression by CD4+CD25+ regulatory T cells in patients with multiple sclerosis. J Exp Med. 2004;199(7):971–9. https://doi.org/10.1084/jem.20031579. Epub 2004/04/07. PubMed PMID: 15067033; PubMed Central PMCID: PMC2211881.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  115. Korn T, Reddy J, Gao W, Bettelli E, Awasthi A, Petersen TR, et al. Myelin-specific regulatory T cells accumulate in the CNS but fail to control autoimmune inflammation. Nat Med. 2007;13(4):423–31. PubMed PMID: 17384649.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  116. Babbe H, Roers A, Waisman A, Lassmann H, Goebels N, Hohlfeld R, et al. Clonal expansions of CD8(+) T cells dominate the T cell infiltrate in active multiple sclerosis lesions as shown by micromanipulation and single cell polymerase chain reaction. J Exp Med. 2000;192(3):393–404. Epub 2000/08/10. PubMed PMID: 10934227; PubMed Central PMCID: PMCPMC2193223.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  117. Schwab N, Bien CG, Waschbisch A, Becker A, Vince GH, Dornmair K, et al. CD8+ T-cell clones dominate brain infiltrates in Rasmussen encephalitis and persist in the periphery. Brain J Neurol. 2009;132(Pt 5):1236–46. https://doi.org/10.1093/brain/awp003. Epub 2009/01/31. PubMed PMID: 19179379.

    Article  Google Scholar 

  118. Schneider-Hohendorf T, Mohan H, Bien CG, Breuer J, Becker A, Gorlich D, et al. CD8(+) T-cell pathogenicity in Rasmussen encephalitis elucidated by large-scale T-cell receptor sequencing. Nat Commun. 2016;7:11153. https://doi.org/10.1038/ncomms11153. Epub 2016/04/05. PubMed PMID: 27040081; PubMed Central PMCID: PMCPMC4822013.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  119. Tzartos JS, Friese MA, Craner MJ, Palace J, Newcombe J, Esiri MM, et al. Interleukin-17 production in central nervous system-infiltrating T cells and glial cells is associated with active disease in multiple sclerosis. Am J Pathol. 2008;172(1):146–55. https://doi.org/10.2353/ajpath.2008.070690. Epub 2007/12/25. PubMed PMID: 18156204; PubMed Central PMCID: PMCPMC2189615.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  120. Intlekofer AM, Banerjee A, Takemoto N, Gordon SM, Dejong CS, Shin H, et al. Anomalous type 17 response to viral infection by CD8+ T cells lacking T-bet and eomesodermin. Science. 2008;321(5887):408–11. https://doi.org/10.1126/science.1159806. Epub 2008/07/19. PubMed PMID: 18635804; PubMed Central PMCID: PMCPMC2807624.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  121. Huber M, Heink S, Pagenstecher A, Reinhard K, Ritter J, Visekruna A, et al. IL-17A secretion by CD8+ T cells supports Th17-mediated autoimmune encephalomyelitis. J Clin Invest. 2013;123(1):247–60. https://doi.org/10.1172/JCI63681. Epub 2012/12/12. PubMed PMID: 23221338; PubMed Central PMCID: PMCPMC3533283.

    Article  CAS  PubMed  Google Scholar 

  122. Quintana E, Fernandez A, Velasco P, de Andres B, Liste I, Sancho D, et al. DNGR-1(+) dendritic cells are located in meningeal membrane and choroid plexus of the noninjured brain. Glia. 2015;63(12):2231–48. https://doi.org/10.1002/glia.22889. Epub 2015/07/18. PubMed PMID: 26184558.

    Article  PubMed  Google Scholar 

  123. Prodinger C, Bunse J, Kruger M, Schiefenhovel F, Brandt C, Laman JD, et al. CD11c-expressing cells reside in the juxtavascular parenchyma and extend processes into the glia limitans of the mouse nervous system. Acta Neuropathol. 2011;121(4):445–58. https://doi.org/10.1007/s00401-010-0774-y. Epub 2010/11/16. PubMed PMID: 21076838.

    Article  CAS  PubMed  Google Scholar 

  124. Greter M, Heppner FL, Lemos MP, Odermatt BM, Goebels N, Laufer T, et al. Dendritic cells permit immune invasion of the CNS in an animal model of multiple sclerosis. Nat Med. 2005;11(3):328–34. https://doi.org/10.1038/nm1197. Epub 2005/03/01. PubMed PMID: 15735653.

    Article  CAS  PubMed  Google Scholar 

  125. McMahon EJ, Bailey SL, Castenada CV, Waldner H, Miller SD. Epitope spreading initiates in the CNS in two mouse models of multiple sclerosis. Nat Med. 2005;11(3):335–9. https://doi.org/10.1038/nm1202. Epub 2005/03/01. PubMed PMID: 15735651.

    Article  CAS  PubMed  Google Scholar 

  126. den Haan JM, Lehar SM, Bevan MJ. CD8(+) but not CD8(−) dendritic cells cross-prime cytotoxic T cells in vivo. J Exp Med. 2000;192(12):1685–96. Epub 2000/12/20. PubMed PMID: 11120766; PubMed Central PMCID: PMCPMC2213493.

    Article  Google Scholar 

  127. Yogev N, Frommer F, Lukas D, Kautz-Neu K, Karram K, Ielo D, et al. Dendritic cells ameliorate autoimmunity in the CNS by controlling the homeostasis of PD-1 receptor(+) regulatory T cells. Immunity. 2012;37(2):264–75. https://doi.org/10.1016/j.immuni.2012.05.025. PubMed PMID: 22902234.

    Article  CAS  PubMed  Google Scholar 

  128. Bailey SL, Schreiner B, McMahon EJ, Miller SD. CNS myeloid DCs presenting endogenous myelin peptides ‘preferentially’ polarize CD4+ T (H)-17 cells in relapsing EAE. Nat Immunol. 2007;8(2):172–80. https://doi.org/10.1038/ni1430. Epub 2007/01/09. PubMed PMID: 17206145.

    Article  CAS  PubMed  Google Scholar 

  129. King IL, Dickendesher TL, Segal BM. Circulating Ly-6C+ myeloid precursors migrate to the CNS and play a pathogenic role during autoimmune demyelinating disease. Blood. 2009;113(14):3190–7. https://doi.org/10.1182/blood-2008-07-168575. Epub 2009/02/07. PubMed PMID: 19196868; PubMed Central PMCID: PMCPMC2665891.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  130. Irla M, Kupfer N, Suter T, Lissilaa R, Benkhoucha M, Skupsky J, et al. MHC class II-restricted antigen presentation by plasmacytoid dendritic cells inhibits T cell-mediated autoimmunity. J Exp Med. 2010;207(9):1891–905. https://doi.org/10.1084/jem.20092627. Epub 2010/08/11. PubMed PMID: 20696698; PubMed Central PMCID: PMCPMC2931160.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  131. Bailey-Bucktrout SL, Caulkins SC, Goings G, Fischer JA, Dzionek A, Miller SD. Cutting edge: central nervous system plasmacytoid dendritic cells regulate the severity of relapsing experimental autoimmune encephalomyelitis. J Immunol. 2008;180(10):6457–61. Epub 2008/05/06. PubMed PMID: 18453561; PubMed Central PMCID: PMCPMC2846244.

    Article  CAS  PubMed  Google Scholar 

  132. Ji Q, Castelli L, Goverman JM. MHC class I-restricted myelin epitopes are cross-presented by Tip-DCs that promote determinant spreading to CD8(+) T cells. Nat Immunol. 2013;14(3):254–61. https://doi.org/10.1038/ni.2513. Epub 2013/01/08. PubMed PMID: 23291597; PubMed Central PMCID: PMCPMC3581685.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  133. Duraes FV, Lippens C, Steinbach K, Dubrot J, Brighouse D, Bendriss-Vermare N, et al. pDC therapy induces recovery from EAE by recruiting endogenous pDC to sites of CNS inflammation. J Autoimmun. 2016;67:8–18. https://doi.org/10.1016/j.jaut.2015.08.014. PubMed PMID: 26341385; PubMed Central PMCID: PMCPMC4758828.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  134. Link H, Huang YM. Oligoclonal bands in multiple sclerosis cerebrospinal fluid: an update on methodology and clinical usefulness. J Neuroimmunol. 2006;180(1–2):17–28. https://doi.org/10.1016/j.jneuroim.2006.07.006. Epub 2006/09/02. PubMed PMID: 16945427.

    Article  CAS  PubMed  Google Scholar 

  135. Mathey EK, Derfuss T, Storch MK, Williams KR, Hales K, Woolley DR, et al. Neurofascin as a novel target for autoantibody-mediated axonal injury. J Exp Med. 2007;204(10):2363–72. https://doi.org/10.1084/jem.20071053. Epub 2007/09/12. PubMed PMID: 17846150; PubMed Central PMCID: PMCPMC2118456.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  136. Lehmann-Horn K, Kinzel S, Weber MS. Deciphering the role of B cells in multiple sclerosis-towards specific targeting of pathogenic function. Int J Mol Sci. 2017;18(10). https://doi.org/10.3390/ijms18102048. Epub 2017/09/28. PubMed PMID: 28946620; PubMed Central PMCID: PMCPMC5666730.

  137. Staun-Ram E, Miller A. Effector and regulatory B cells in multiple sclerosis. Clin Immunol. 2017;184:11–25. https://doi.org/10.1016/j.clim.2017.04.014. Epub 2017/05/04. PubMed PMID: 28461106.

    Article  CAS  PubMed  Google Scholar 

  138. Waters P, Jarius S, Littleton E, Leite MI, Jacob S, Gray B, et al. Aquaporin-4 antibodies in neuromyelitis optica and longitudinally extensive transverse myelitis. Arch Neurol. 2008;65(7):913–9. https://doi.org/10.1001/archneur.65.7.913. Epub 2008/07/16. PubMed PMID: 18625857.

    Article  PubMed  Google Scholar 

  139. Yick LW, Ma OK, Ng RC, Kwan JS, Chan KH. Aquaporin-4 autoantibodies from neuromyelitis optica spectrum disorder patients induce complement-independent immunopathologies in mice. Front Immunol. 2018;9:1438. https://doi.org/10.3389/fimmu.2018.01438. Epub 2018/07/11. PubMed PMID: 29988553; PubMed Central PMCID: PMCPMC6026644.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  140. Hinson SR, Romero MF, Popescu BF, Lucchinetti CF, Fryer JP, Wolburg H, et al. Molecular outcomes of neuromyelitis optica (NMO)-IgG binding to aquaporin-4 in astrocytes. Proc Natl Acad Sci U S A. 2012;109(4):1245–50. https://doi.org/10.1073/pnas.1109980108. Epub 2011/12/01. PubMed PMID: 22128336; PubMed Central PMCID: PMCPMC3268278.

    Article  PubMed  Google Scholar 

  141. Vaknin-Dembinsky A, Brill L, Kassis I, Petrou P, Ovadia H, Ben-Hur T, et al. T-cell responses to distinct AQP4 peptides in patients with neuromyelitis optica (NMO). Mult Scler Relat Disord. 2016;6:28–36. https://doi.org/10.1016/j.msard.2015.12.004. Epub 2016/04/12. PubMed PMID: 27063619.

    Article  PubMed  Google Scholar 

  142. Kothur K, Wienholt L, Tantsis EM, Earl J, Bandodkar S, Prelog K, et al. B cell, Th17, and neutrophil related cerebrospinal fluid cytokine/chemokines are elevated in MOG antibody associated demyelination. PLoS One. 2016;11(2):e0149411. https://doi.org/10.1371/journal.pone.0149411. Epub 2016/02/27. PubMed PMID: 26919719; PubMed Central PMCID: PMCPMC4769285.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  143. Pohl-Koppe A, Burchett SK, Thiele EA, Hafler DA. Myelin basic protein reactive Th2 T cells are found in acute disseminated encephalomyelitis. J Neuroimmunol. 1998;91(1–2):19–27. Epub 1998/12/10. PubMed PMID: 9846815.

    Article  CAS  PubMed  Google Scholar 

  144. Manto M, Honnorat J, Hampe CS, Guerra-Narbona R, Lopez-Ramos JC, Delgado-Garcia JM, et al. Disease-specific monoclonal antibodies targeting glutamate decarboxylase impair GABAergic neurotransmission and affect motor learning and behavioral functions. Front Behav Neurosci. 2015;9:78. https://doi.org/10.3389/fnbeh.2015.00078. Epub 2015/04/15. PubMed PMID: 25870548; PubMed Central PMCID: PMCPMC4375997.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  145. Skorstad G, Hestvik AL, Vartdal F, Holmoy T. Cerebrospinal fluid T cell responses against glutamic acid decarboxylase 65 in patients with stiff person syndrome. J Autoimmun. 2009;32(1):24–32. https://doi.org/10.1016/j.jaut.2008.10.002. Epub 2008/11/26. PubMed PMID: 19027267.

    Article  CAS  PubMed  Google Scholar 

  146. Dalmau J, Gleichman AJ, Hughes EG, Rossi JE, Peng X, Lai M, et al. Anti-NMDA-receptor encephalitis: case series and analysis of the effects of antibodies. Lancet Neurol. 2008;7(12):1091–8. https://doi.org/10.1016/S1474-4422(08)70224-2. Epub 2008/10/15. PubMed PMID: 18851928; PubMed Central PMCID: PMCPMC2607118.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  147. Hughes EG, Peng X, Gleichman AJ, Lai M, Zhou L, Tsou R, et al. Cellular and synaptic mechanisms of anti-NMDA receptor encephalitis. J Neurosci Off J Soc Neurosci. 2010;30(17):5866–75. https://doi.org/10.1523/JNEUROSCI.0167-10.2010. Epub 2010/04/30. PubMed PMID: 20427647; PubMed Central PMCID: PMCPMC2868315.

    Article  CAS  Google Scholar 

  148. Lai M, Hughes EG, Peng X, Zhou L, Gleichman AJ, Shu H, et al. AMPA receptor antibodies in limbic encephalitis alter synaptic receptor location. Ann Neurol. 2009;65(4):424–34. https://doi.org/10.1002/ana.21589. Epub 2009/04/02. PubMed PMID: 19338055; PubMed Central PMCID: PMCPMC2677127.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  149. Ohkawa T, Satake S, Yokoi N, Miyazaki Y, Ohshita T, Sobue G, et al. Identification and characterization of GABA(A) receptor autoantibodies in autoimmune encephalitis. J Neurosci Off J Soc Neurosci. 2014;34(24):8151–63. https://doi.org/10.1523/JNEUROSCI.4415-13.2014. Epub 2014/06/13. PubMed PMID: 24920620.

    Article  CAS  Google Scholar 

  150. Moscato EH, Peng X, Jain A, Parsons TD, Dalmau J, Balice-Gordon RJ. Acute mechanisms underlying antibody effects in anti-N-methyl-D-aspartate receptor encephalitis. Ann Neurol. 2014;76(1):108–19. https://doi.org/10.1002/ana.24195. Epub 2014/06/12. PubMed PMID: 24916964; PubMed Central PMCID: PMCPMC4296347.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  151. Peng X, Hughes EG, Moscato EH, Parsons TD, Dalmau J, Balice-Gordon RJ. Cellular plasticity induced by anti-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor encephalitis antibodies. Ann Neurol. 2015;77(3):381–98. https://doi.org/10.1002/ana.24293. Epub 2014/11/05. PubMed PMID: 25369168; PubMed Central PMCID: PMCPMC4365686.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  152. Ohkawa T, Fukata Y, Yamasaki M, Miyazaki T, Yokoi N, Takashima H, et al. Autoantibodies to epilepsy-related LGI1 in limbic encephalitis neutralize LGI1-ADAM22 interaction and reduce synaptic AMPA receptors. J Neurosci Off J Soc Neurosci. 2013;33(46):18161–74. https://doi.org/10.1523/JNEUROSCI.3506-13.2013. Epub 2013/11/15. PubMed PMID: 24227725; PubMed Central PMCID: PMCPMC3828467.

    Article  CAS  Google Scholar 

  153. Carvajal-Gonzalez A, Leite MI, Waters P, Woodhall M, Coutinho E, Balint B, et al. Glycine receptor antibodies in PERM and related syndromes: characteristics, clinical features and outcomes. Brain J Neurol. 2014;137(Pt 8):2178–92. https://doi.org/10.1093/brain/awu142. Epub 2014/06/22. PubMed PMID: 24951641; PubMed Central PMCID: PMCPMC4107739.

    Article  Google Scholar 

  154. Klein RS, Hunter CA. Protective and pathological immunity during central nervous system infections. Immunity. 2017;46(6):891–909. https://doi.org/10.1016/j.immuni.2017.06.012. Epub 2017/06/22. PubMed PMID: 28636958.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  155. Coureuil M, Lecuyer H, Scott MG, Boularan C, Enslen H, Soyer M, et al. Meningococcus Hijacks a beta2-adrenoceptor/beta-Arrestin pathway to cross brain microvasculature endothelium. Cell. 2010;143(7):1149–60. https://doi.org/10.1016/j.cell.2010.11.035. Epub 2010/12/25. PubMed PMID: 21183077.

    Article  CAS  PubMed  Google Scholar 

  156. Tripathi AK, Sha W, Shulaev V, Stins MF, Sullivan DJ Jr. Plasmodium falciparum-infected erythrocytes induce NF-kappaB regulated inflammatory pathways in human cerebral endothelium. Blood. 2009;114(19):4243–52. https://doi.org/10.1182/blood-2009-06-226415. Epub 2009/08/29. PubMed PMID: 19713460; PubMed Central PMCID: PMCPMC2925626.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  157. Reinert LS, Lopusna K, Winther H, Sun C, Thomsen MK, Nandakumar R, et al. Sensing of HSV-1 by the cGAS-STING pathway in microglia orchestrates antiviral defence in the CNS. Nat Commun. 2016;7:13348. https://doi.org/10.1038/ncomms13348. Epub 2016/11/11. PubMed PMID: 27830700; PubMed Central PMCID: PMCPMC5109551.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  158. Mukherjee P, Woods TA, Moore RA, Peterson KE. Activation of the innate signaling molecule MAVS by bunyavirus infection upregulates the adaptor protein SARM1, leading to neuronal death. Immunity. 2013;38(4):705–16. https://doi.org/10.1016/j.immuni.2013.02.013. Epub 2013/03/19. PubMed PMID: 23499490; PubMed Central PMCID: PMCPMC4783152.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  159. Louveau A, Herz J, Alme MN, Salvador AF, Dong MQ, Viar KE, et al. CNS lymphatic drainage and neuroinflammation are regulated by meningeal lymphatic vasculature. Nat Neurosci. 2018;21(10):1380–91. https://doi.org/10.1038/s41593-018-0227-9. Epub 2018/09/19. PubMed PMID: 30224810.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  160. Durrant DM, Robinette ML, Klein RS. IL-1R1 is required for dendritic cell-mediated T cell reactivation within the CNS during West Nile virus encephalitis. J Exp Med. 2013;210(3):503–16. https://doi.org/10.1084/jem.20121897. Epub 2013/03/06. PubMed PMID: 23460727; PubMed Central PMCID: PMCPMC3600909.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  161. Kim JV, Kang SS, Dustin ML, McGavern DB. Myelomonocytic cell recruitment causes fatal CNS vascular injury during acute viral meningitis. Nature. 2009;457(7226):191–5. https://doi.org/10.1038/nature07591. Epub 2008/11/18. PubMed PMID: 19011611; PubMed Central PMCID: PMCPMC2702264.

    Article  CAS  PubMed  Google Scholar 

  162. Wakim LM, Woodward-Davis A, Bevan MJ. Memory T cells persisting within the brain after local infection show functional adaptations to their tissue of residence. Proc Natl Acad Sci U S A. 2010;107(42):17872–9. https://doi.org/10.1073/pnas.1010201107. Epub 2010/10/07. PubMed PMID: 20923878; PubMed Central PMCID: PMCPMC2964240.

    Article  PubMed Central  PubMed  Google Scholar 

  163. Trandem K, Zhao J, Fleming E, Perlman S. Highly activated cytotoxic CD8 T cells express protective IL-10 at the peak of coronavirus-induced encephalitis. J Immunol. 2011;186(6):3642–52. https://doi.org/10.4049/jimmunol.1003292. Epub 2011/02/15. PubMed PMID: 21317392; PubMed Central PMCID: PMCPMC3063297.

    Article  CAS  PubMed  Google Scholar 

  164. Stumhofer JS, Laurence A, Wilson EH, Huang E, Tato CM, Johnson LM, et al. Interleukin 27 negatively regulates the development of interleukin 17-producing T helper cells during chronic inflammation of the central nervous system. Nat Immunol. 2006;7(9):937–45. https://doi.org/10.1038/ni1376. Epub 2006/08/15. PubMed PMID: 16906166.

    Article  CAS  PubMed  Google Scholar 

  165. Zhao J, Zhao J, Perlman S. Virus-specific regulatory T cells ameliorate encephalitis by repressing effector T cell functions from priming to effector stages. PLoS Pathog. 2014;10(8):e1004279. https://doi.org/10.1371/journal.ppat.1004279. Epub 2014/08/08. PubMed PMID: 25102154; PubMed Central PMCID: PMCPMC4125232.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  166. Yuki N, Susuki K, Koga M, Nishimoto Y, Odaka M, Hirata K, et al. Carbohydrate mimicry between human ganglioside GM1 and Campylobacter jejuni lipooligosaccharide causes Guillain-Barre syndrome. Proc Natl Acad Sci U S A. 2004;101(31):11404–9. https://doi.org/10.1073/pnas.0402391101. Epub 2004/07/28. PubMed PMID: 15277677; PubMed Central PMCID: PMCPMC509213.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  167. Avril T, Wagner ER, Willison HJ, Crocker PR. Sialic acid-binding immunoglobulin-like lectin 7 mediates selective recognition of sialylated glycans expressed on Campylobacter jejuni lipooligosaccharides. Infect Immun. 2006;74(7):4133–41. https://doi.org/10.1128/IAI.02094-05. Epub 2006/06/23. PubMed PMID: 16790787; PubMed Central PMCID: PMCPMC1489752.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  168. Jung S, Zimmer S, Luneberg E, Frosch M, Karch H, Korn T, et al. Lipooligosaccharide of Campylobacter jejuni prevents myelin-specific enteral tolerance to autoimmune neuritis – a potential mechanism in Guillain-Barre syndrome? Neurosci Lett. 2005;381(1–2):175–8. https://doi.org/10.1016/j.neulet.2005.02.028. Epub 2005/05/11. PubMed PMID: 15882812.

    Article  CAS  PubMed  Google Scholar 

  169. Wakerley BR, Yuki N. Infectious and noninfectious triggers in Guillain-Barre syndrome. Expert Rev Clin Immunol. 2013;9(7):627–39. https://doi.org/10.1586/1744666X.2013.811119. Epub 2013/08/01. PubMed PMID: 23899233.

    Article  CAS  PubMed  Google Scholar 

  170. Cooper JC, Hughes S, Ben-Smith A, Savage CO, Winer JB. T cell recognition of a non-protein antigen preparation of Campylobacter jejuni in patients with Guillain-Barre syndrome. J Neurol Neurosurg Psychiatry. 2002;72(3):413–4. Epub 2002/02/28. PubMed PMID: 11861714; PubMed Central PMCID: PMCPMC1737765.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  171. Wang X, Zheng XY, Ma C, Wang XK, Wu J, Adem A, et al. Mitigated Tregs and augmented Th17 cells and cytokines are associated with severity of experimental autoimmune neuritis. Scand J Immunol. 2014;80(3):180–90. https://doi.org/10.1111/sji.12201. Epub 2014/06/10. PubMed PMID: 24910360.

    Article  CAS  PubMed  Google Scholar 

  172. Ambrosius B, Pitarokoili K, Schrewe L, Pedreiturria X, Motte J, Gold R. Fingolimod attenuates experimental autoimmune neuritis and contributes to Schwann cell-mediated axonal protection. J Neuroinflammation. 2017;14(1):92. https://doi.org/10.1186/s12974-017-0864-z. Epub 2017/04/28. PubMed PMID: 28446186; PubMed Central PMCID: PMCPMC5406994.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  173. Fagone P, Mazzon E, Chikovani T, Saraceno A, Mammana S, Colletti G, et al. Decitabine induces regulatory T cells, inhibits the production of IFN-gamma and IL-17 and exerts preventive and therapeutic efficacy in rodent experimental autoimmune neuritis. J Neuroimmunol. 2018;321:41–8. https://doi.org/10.1016/j.jneuroim.2018.05.013. Epub 2018/06/30. PubMed PMID: 29957387.

    Article  CAS  PubMed  Google Scholar 

  174. Nakamura K, Irie S, Kanazawa N, Saito T, Tamai Y. Anti-GM2 antibodies in Guillain-Barre syndrome with acute cytomegalovirus infection. Ann N Y Acad Sci. 1998;845:423. Epub 1998/07/21. PubMed PMID: 9668386.

    Article  CAS  PubMed  Google Scholar 

  175. Pangault C, Le Tulzo Y, Minjolle S, Le Page E, Sebti Y, Guilloux V, et al. HLA-G expression in Guillain-Barre syndrome is associated with primary infection with cytomegalovirus. Viral Immunol. 2004;17(1):123–5. https://doi.org/10.1089/088282404322875520. Epub 2004/03/17. PubMed PMID: 15018669.

    Article  CAS  PubMed  Google Scholar 

  176. Schnorf H, Rathgeb JP, Kohler A. Anti-GQ1b-positive Miller Fisher syndrome in a patient with acute Epstein-Barr virus infection and negative Campylobacter serology. Eur Neurol. 1998;40(3):177. Epub 1999/02/20. PubMed PMID: 10026022.

    CAS  PubMed  Google Scholar 

  177. Maurissen I, Jeurissen A, Strauven T, Sprengers D, De Schepper B. First case of anti-ganglioside GM1-positive Guillain-Barre syndrome due to hepatitis E virus infection. Infection. 2012;40(3):323–6. https://doi.org/10.1007/s15010-011-0185-6. Epub 2011/08/31. PubMed PMID: 21877179.

    Article  CAS  PubMed  Google Scholar 

  178. Kornreich L, Shkalim-Zemer V, Levinsky Y, Abdallah W, Ganelin-Cohen E, Straussberg R. Acute Cerebellitis in children: a many-faceted disease. J Child Neurol. 2016;31(8):991–7. https://doi.org/10.1177/0883073816634860. Epub 2016/03/11. PubMed PMID: 26961264.

    Article  PubMed  Google Scholar 

  179. Desai J, Mitchell WG. Acute cerebellar ataxia, acute cerebellitis, and opsoclonus-myoclonus syndrome. J Child Neurol. 2012;27(11):1482–8. https://doi.org/10.1177/0883073812450318. Epub 2012/07/19. PubMed PMID: 22805251.

    Article  PubMed  Google Scholar 

  180. Melms A, Luther C, Stoeckle C, Poschel S, Schroth P, Varga M, et al. Thymus and myasthenia gravis: antigen processing in the human thymus and the consequences for the generation of autoreactive T cells. Acta Neurol Scand Suppl. 2006;183:12–3. https://doi.org/10.1111/j.1600-0404.2006.00636.x. Epub 2006/04/28. PubMed PMID: 16637920.

    Article  CAS  PubMed  Google Scholar 

  181. Nagvekar N, Moody AM, Moss P, Roxanis I, Curnow J, Beeson D, et al. A pathogenetic role for the thymoma in myasthenia gravis. Autosensitization of IL-4- producing T cell clones recognizing extracellular acetylcholine receptor epitopes presented by minority class II isotypes. J Clin Invest. 1998;101(10):2268–77. https://doi.org/10.1172/JCI2068. Epub 1998/05/29. PubMed PMID: 9593783; PubMed Central PMCID: PMCPMC508815.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  182. Alvarez Arias DA, Kim HJ, Zhou P, Holderried TA, Wang X, Dranoff G, et al. Disruption of CD8+ Treg activity results in expansion of T follicular helper cells and enhanced antitumor immunity. Cancer Immunol Res. 2014;2(3):207–16. https://doi.org/10.1158/2326-6066.Cir-13-0121. Epub 2014/04/30. PubMed PMID: 24778317; PubMed Central PMCID: PMCPMC4217219.

    Article  CAS  PubMed  Google Scholar 

  183. McKeon A, Pittock SJ. Paraneoplastic encephalomyelopathies: pathology and mechanisms. Acta Neuropathol. 2011;122(4):381–400. https://doi.org/10.10007/s00401-011-0876-1. Epub 2011/09/23. PubMed PMID: 21938556.

    Article  CAS  PubMed  Google Scholar 

  184. Barile-Fabris L, Hernandez-Cabrera MF, Barragan-Garfias JA. Vasculitis in systemic lupus erythematosus. Curr Rheumatol Rep. 2014;16(9):440. https://doi.org/10.1007/s11926-014-0440-9. Epub 2014/07/16. PubMed PMID: 25023725.

    Article  CAS  PubMed  Google Scholar 

  185. Wu F, Liu L, Zhou H. Endothelial cell activation in central nervous system inflammation. J Leukoc Biol. 2017;101(5):1119–32. https://doi.org/10.1189/jlb.3RU0816-352RR. Epub 2017/02/16. PubMed PMID: 28196850.

    Article  CAS  PubMed  Google Scholar 

  186. Argaw AT, Asp L, Zhang J, Navrazhina K, Pham T, Mariani JN, et al. Astrocyte-derived VEGF-A drives blood-brain barrier disruption in CNS inflammatory disease. J Clin Invest. 2012;122(7):2454–68. https://doi.org/10.1172/JCI60842. Epub 2012/06/02. PubMed PMID: 22653056; PubMed Central PMCID: PMC3386814.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  187. Ohlin KE, Francardo V, Lindgren HS, Sillivan SE, O’Sullivan SS, Luksik AS, et al. Vascular endothelial growth factor is upregulated by L-dopa in the parkinsonian brain: implications for the development of dyskinesia. Brain J Neurol. 2011;134(Pt 8):2339–57. https://doi.org/10.1093/brain/awr165. Epub 2011/07/21. PubMed PMID: 21771855; PubMed Central PMCID: PMCPMC3155708.

    Article  Google Scholar 

  188. LeWitt PA, Hauser RA, Pahwa R, Isaacson SH, Fernandez HH, Lew M, et al. Safety and efficacy of CVT-301 (levodopa inhalation powder) on motor function during off periods in patients with Parkinson’s disease: a randomised, double-blind, placebo-controlled phase 3 trial. Lancet Neurol. 2019;18(2):145–54. https://doi.org/10.1016/S1474-4422(18)30405-8. Epub 2019/01/22. PubMed PMID: 30663606.

    Article  CAS  PubMed  Google Scholar 

  189. Birukova AA, Zagranichnaya T, Fu P, Alekseeva E, Chen W, Jacobson JR, et al. Prostaglandins PGE(2) and PGI(2) promote endothelial barrier enhancement via PKA- and Epac1/Rap1-dependent Rac activation. Exp Cell Res. 2007;313(11):2504–20. https://doi.org/10.1016/j.yexcr.2007.03.036. Epub 2007/05/12. PubMed PMID: 17493609; PubMed Central PMCID: PMCPMC1974901.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  190. Heneka MT, Kummer MP, Latz E. Innate immune activation in neurodegenerative disease. Nat Rev Immunol. 2014;14(7):463–77. https://doi.org/10.1038/nri3705. Epub 2014/06/26. PubMed PMID: 24962261.

    Article  CAS  PubMed  Google Scholar 

  191. Hollingworth P, Harold D, Sims R, Gerrish A, Lambert JC, Carrasquillo MM, et al. Common variants at ABCA7, MS4A6A/MS4A4E, EPHA1, CD33 and CD2AP are associated with Alzheimer’s disease. Nat Genet. 2011;43(5):429–35. https://doi.org/10.1038/ng.803. Epub 2011/04/05. PubMed PMID: 21460840; PubMed Central PMCID: PMCPMC3084173.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  192. Hirsch EC, Hunot S. Neuroinflammation in Parkinson’s disease: a target for neuroprotection? Lancet Neurol. 2009;8(4):382–97. https://doi.org/10.1016/S1474-4422(09)70062-6. Epub 2009/03/20. PubMed PMID: 19296921.

    Article  CAS  PubMed  Google Scholar 

  193. Rayaprolu S, Mullen B, Baker M, Lynch T, Finger E, Seeley WW, et al. TREM2 in neurodegeneration: evidence for association of the p.R47H variant with frontotemporal dementia and Parkinson’s disease. Mol Neurodegener. 2013;8:19. https://doi.org/10.1186/1750-1326-8-19. Epub 2013/06/27. PubMed PMID: 23800361; PubMed Central PMCID: PMCPMC3691612.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  194. Linnartz-Gerlach B, Bodea LG, Klaus C, Ginolhac A, Halder R, Sinkkonen L, et al. TREM2 triggers microglial density and age-related neuronal loss. Glia. 2019;67(3):539–50. https://doi.org/10.1002/glia.23563. Epub 2018/12/15. PubMed PMID: 30548312.

    Article  PubMed  Google Scholar 

  195. Strowig T, Henao-Mejia J, Elinav E, Flavell R. Inflammasomes in health and disease. Nature. 2012;481(7381):278–86. https://doi.org/10.1038/nature10759. Epub 2012/01/20. PubMed PMID: 22258606.

    Article  CAS  PubMed  Google Scholar 

  196. Shastri A, Bonifati DM, Kishore U. Innate immunity and neuroinflammation. Mediat Inflamm. 2013;2013:342931. https://doi.org/10.1155/2013/342931. Epub 2013/07/12. PubMed PMID: 23843682; PubMed Central PMCID: PMCPMC3697414.

    Article  CAS  Google Scholar 

  197. Jonsson T, Stefansson H, Steinberg S, Jonsdottir I, Jonsson PV, Snaedal J, et al. Variant of TREM2 associated with the risk of Alzheimer’s disease. N Engl J Med. 2013;368(2):107–16. https://doi.org/10.1056/NEJMoa1211103. Epub 2012/11/16. PubMed PMID: 23150908; PubMed Central PMCID: PMCPMC3677583.

    Article  CAS  PubMed  Google Scholar 

  198. Heneka MT, Kummer MP, Stutz A, Delekate A, Schwartz S, Vieira-Saecker A, et al. NLRP3 is activated in Alzheimer’s disease and contributes to pathology in APP/PS1 mice. Nature. 2013;493(7434):674–8. https://doi.org/10.1038/nature11729. Epub 2012/12/21. PubMed PMID: 23254930; PubMed Central PMCID: PMCPMC3812809.

    Article  CAS  PubMed  Google Scholar 

  199. Noelker C, Morel L, Lescot T, Osterloh A, Alvarez-Fischer D, Breloer M, et al. Toll like receptor 4 mediates cell death in a mouse MPTP model of Parkinson disease. Sci Rep. 2013;3:1393. https://doi.org/10.1038/srep01393. Epub 2013/03/07. PubMed PMID: 23462811; PubMed Central PMCID: PMCPMC3589722.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  200. Frakes AE, Ferraiuolo L, Haidet-Phillips AM, Schmelzer L, Braun L, Miranda CJ, et al. Microglia induce motor neuron death via the classical NF-kappaB pathway in amyotrophic lateral sclerosis. Neuron. 2014;81(5):1009–23. https://doi.org/10.1016/j.neuron.2014.01.013. Epub 2014/03/13. PubMed PMID: 24607225; PubMed Central PMCID: PMCPMC3978641.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  201. Kefalakes E, Boselt S, Sarikidi A, Ettcheto M, Bursch F, Naujock M, et al. Characterizing the multiple roles of FGF-2 in SOD1(G93A) ALS mice in vivo and in vitro. J Cell Physiol. 2019;234(5):7395–410. https://doi.org/10.1002/jcp.27498. Epub 2018/10/30. PubMed PMID: 30370540.

    Article  CAS  PubMed  Google Scholar 

  202. Grottelli S, Mezzasoma L, Scarpelli P, Cacciatore I, Cellini B, Bellezza I. Cyclo(His-Pro) inhibits NLRP3 inflammasome cascade in ALS microglial cells. Mol Cell Neurosci. 2019;94:23–31. https://doi.org/10.1016/j.mcn.2018.11.002. Epub 2018/11/16. PubMed PMID: 30439413.

    Article  CAS  PubMed  Google Scholar 

  203. Schutz B, Reimann J, Dumitrescu-Ozimek L, Kappes-Horn K, Landreth GE, Schurmann B, et al. The oral antidiabetic pioglitazone protects from neurodegeneration and amyotrophic lateral sclerosis-like symptoms in superoxide dismutase-G93A transgenic mice. J Neurosci Off J Soc Neurosci. 2005;25(34):7805–12. https://doi.org/10.1523/JNEUROSCI.2038-05.2005. Epub 2005/08/27. PubMed PMID: 16120782.

    Article  CAS  Google Scholar 

  204. Kiaei M, Kipiani K, Chen J, Calingasan NY, Beal MF. Peroxisome proliferator-activated receptor-gamma agonist extends survival in transgenic mouse model of amyotrophic lateral sclerosis. Exp Neurol. 2005;191(2):331–6. https://doi.org/10.1016/j.expneurol.2004.10.007. Epub 2005/01/15. PubMed PMID: 15649489.

    Article  CAS  PubMed  Google Scholar 

  205. Singhrao SK, Neal JW, Morgan BP, Gasque P. Increased complement biosynthesis by microglia and complement activation on neurons in Huntington’s disease. Exp Neurol. 1999;159(2):362–76. https://doi.org/10.1006/exnr.1999.7170. Epub 1999/10/03. PubMed PMID: 10506508.

    Article  CAS  PubMed  Google Scholar 

  206. Palazuelos J, Aguado T, Pazos MR, Julien B, Carrasco C, Resel E, et al. Microglial CB2 cannabinoid receptors are neuroprotective in Huntington’s disease excitotoxicity. Brain J Neurol. 2009;132(Pt 11):3152–64. https://doi.org/10.1093/brain/awp239. Epub 2009/10/07. PubMed PMID: 19805493.

    Article  Google Scholar 

  207. Bradford J, Shin JY, Roberts M, Wang CE, Li XJ, Li S. Expression of mutant huntingtin in mouse brain astrocytes causes age-dependent neurological symptoms. Proc Natl Acad Sci U S A. 2009;106(52):22480–5. https://doi.org/10.1073/pnas.0911503106. Epub 2009/12/19. PubMed PMID: 20018729; PubMed Central PMCID: PMCPMC2799722.

    Article  PubMed Central  PubMed  Google Scholar 

  208. Shin JY, Fang ZH, Yu ZX, Wang CE, Li SH, Li XJ. Expression of mutant huntingtin in glial cells contributes to neuronal excitotoxicity. J Cell Biol. 2005;171(6):1001–12. https://doi.org/10.1083/jcb.200508072. Epub 2005/12/21. PubMed PMID: 16365166; PubMed Central PMCID: PMCPMC2171327.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  209. Mosley RL. Adaptive immunity in neurodegenerative and neuropsychological disorders. J Neuroimmune Pharmacol. 2015;10(4):522–7. https://doi.org/10.1007/s11481-015-9640-y. Epub 2015/10/27. PubMed PMID: 26496777.

    Article  PubMed  Google Scholar 

  210. Baruch K, Rosenzweig N, Kertser A, Deczkowska A, Sharif AM, Spinrad A, et al. Breaking immune tolerance by targeting Foxp3(+) regulatory T cells mitigates Alzheimer’s disease pathology. Nat Commun. 2015;6:7967. https://doi.org/10.1038/ncomms8967. Epub 2015/08/19. PubMed PMID: 26284939; PubMed Central PMCID: PMCPMC4557123.

    Article  CAS  PubMed  Google Scholar 

  211. Ghochikyan A, Mkrtichyan M, Petrushina I, Movsesyan N, Karapetyan A, Cribbs DH, et al. Prototype Alzheimer’s disease epitope vaccine induced strong Th2-type anti-Abeta antibody response with Alum to Quil A adjuvant switch. Vaccine. 2006;24(13):2275–82. https://doi.org/10.1016/j.vaccine.2005.11.039. Epub 2005/12/22. PubMed PMID: 16368167; PubMed Central PMCID: PMCPMC2081151.

    Article  CAS  PubMed  Google Scholar 

  212. McManus RM, Mills KH, Lynch MA. T cells-protective or pathogenic in Alzheimer’s disease? J Neuroimmune Pharmacol. 2015;10(4):547–60. https://doi.org/10.1007/s11481-015-9612-2. Epub 2015/05/11. PubMed PMID: 25957956.

    Article  PubMed  Google Scholar 

  213. Blomstrom A, Karlsson H, Gardner R, Jorgensen L, Magnusson C, Dalman C. Associations between maternal infection during pregnancy, childhood infections, and the risk of subsequent psychotic disorder – a Swedish Cohort Study of nearly 2 million individuals. Schizophr Bull. 2016;42(1):125–33. https://doi.org/10.1093/schbul/sbv112. Epub 2015/08/26. PubMed PMID: 26303935; PubMed Central PMCID: PMCPMC4681563.

    Article  PubMed  Google Scholar 

  214. Knuesel I, Chicha L, Britschgi M, Schobel SA, Bodmer M, Hellings JA, et al. Maternal immune activation and abnormal brain development across CNS disorders. Nat Rev Neurol. 2014;10(11):643–60. https://doi.org/10.1038/nrneurol.2014.187. Epub 2014/10/15. PubMed PMID: 25311587.

    Article  CAS  PubMed  Google Scholar 

  215. Estes ML, McAllister AK. Maternal immune activation: implications for neuropsychiatric disorders. Science. 2016;353(6301):772–7. https://doi.org/10.1126/science.aag3194. Epub 2016/08/20. PubMed PMID: 27540164; PubMed Central PMCID: PMCPMC5650490.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  216. Meyer U. Prenatal poly(i:C) exposure and other developmental immune activation models in rodent systems. Biol Psychiatry. 2014;75(4):307–15. https://doi.org/10.1016/j.biopsych.2013.07.011. Epub 2013/08/14. PubMed PMID: 23938317.. PubMed PMID: 23938317.

    Article  CAS  PubMed  Google Scholar 

  217. Coutinho E, Vincent A. Autoimmunity in neuropsychiatric disorders. Handb Clin Neurol. 2016;133:269–82. https://doi.org/10.1016/B978-0-444-63432-0.00015-3. Epub 2016/04/27. PubMed PMID: 27112682.

    Article  PubMed  Google Scholar 

  218. Brimberg L, Sadiq A, Gregersen PK, Diamond B. Brain-reactive IgG correlates with autoimmunity in mothers of a child with an autism spectrum disorder. Mol Psychiatry. 2013;18(11):1171–7. https://doi.org/10.1038/mp.2013.101. Epub 2013/08/21. PubMed PMID: 23958959.

    Article  CAS  PubMed  Google Scholar 

  219. Braunschweig D, Golub MS, Koenig CM, Qi L, Pessah IN, Van de Water J, et al. Maternal autism-associated IgG antibodies delay development and produce anxiety in a mouse gestational transfer model. J Neuroimmunol. 2012;252(1–2):56–65. https://doi.org/10.1016/j.jneuroim.2012.08.002. Epub 2012/09/07. PubMed PMID: 22951357; PubMed Central PMCID: PMCPMC4096980.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  220. Martin LA, Ashwood P, Braunschweig D, Cabanlit M, Van de Water J, Amaral DG. Stereotypies and hyperactivity in rhesus monkeys exposed to IgG from mothers of children with autism. Brain Behav Immun. 2008;22(6):806–16. https://doi.org/10.1016/j.bbi.2007.12.007. Epub 2008/02/12. PubMed PMID: 18262386; PubMed Central PMCID: PMCPMC3779644.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  221. Gao R, Penzes P. Common mechanisms of excitatory and inhibitory imbalance in schizophrenia and autism spectrum disorders. Curr Mol Med. 2015;15(2):146–67. Epub 2015/03/04. PubMed PMID: 25732149; PubMed Central PMCID: PMCPMC4721588.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  222. Choi GB, Yim YS, Wong H, Kim S, Kim H, Kim SV, et al. The maternal interleukin-17a pathway in mice promotes autism-like phenotypes in offspring. Science. 2016;351(6276):933–9. https://doi.org/10.1126/science.aad0314. Epub 2016/01/30. PubMed PMID: 26822608; PubMed Central PMCID: PMCPMC4782964.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  223. Baptista TSA, Petersen LE, Molina JK, de Nardi T, Wieck A, do Prado A, et al. Autoantibodies against myelin sheath and S100beta are associated with cognitive dysfunction in patients with rheumatoid arthritis. Clin Rheumatol. 2017;36(9):1959–68. https://doi.org/10.1007/s10067-017-3724-4. Epub 2017/06/29. PubMed PMID: 28656478.

    Article  PubMed  Google Scholar 

  224. DeGiorgio LA, Konstantinov KN, Lee SC, Hardin JA, Volpe BT, Diamond B. A subset of lupus anti-DNA antibodies cross-reacts with the NR2 glutamate receptor in systemic lupus erythematosus. Nat Med. 2001;7(11):1189–93. https://doi.org/10.1038/nm1101-1189. Epub 2001/11/02. PubMed PMID: 11689882.

    Article  CAS  PubMed  Google Scholar 

  225. Kowal C, Degiorgio LA, Lee JY, Edgar MA, Huerta PT, Volpe BT, et al. Human lupus autoantibodies against NMDA receptors mediate cognitive impairment. Proc Natl Acad Sci U S A. 2006;103(52):19854–9. https://doi.org/10.1073/pnas.0608397104. Epub 2006/12/16. PubMed PMID: 17170137; PubMed Central PMCID: PMCPMC1702320.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  226. Kim R, Healey KL, Sepulveda-Orengo MT, Reissner KJ. Astroglial correlates of neuropsychiatric disease: from astrocytopathy to astrogliosis. Prog Neuro-Psychopharmacol Biol Psychiatry. 2018;87(Pt A):126–46. https://doi.org/10.1016/j.pnpbp.2017.10.002. Epub 2017/10/11. PubMed PMID: 28989099; PubMed Central PMCID: PMCPMC5889368.

    Article  Google Scholar 

  227. McKeon A. Immunotherapeutics for autoimmune encephalopathies and dementias. Curr Treat Options Neurol. 2013;15(6):723–37. https://doi.org/10.1007/s11940-013-0251-8. Epub 2013/06/15. PubMed PMID: 23765510.

    Article  PubMed  Google Scholar 

  228. Szabo SJ, Kim ST, Costa GL, Zhang X, Fathman CG, Glimcher LH. A novel transcription factor, T-bet, directs Th1 lineage commitment. Cell. 2000;100(6):655–69. PubMed PMID: 10761931.

    Article  CAS  PubMed  Google Scholar 

  229. McGeachy MJ, Bak-Jensen KS, Chen Y, Tato CM, Blumenschein W, McClanahan T, et al. TGF-beta and IL-6 drive the production of IL-17 and IL-10 by T cells and restrain T(H)-17 cell-mediated pathology. Nat Immunol. 2007;8(12):1390–7. https://doi.org/10.1038/ni1539. PubMed PMID: 17994024.

    Article  CAS  PubMed  Google Scholar 

  230. Peters A, Lee Y, Kuchroo VK. The many faces of Th17 cells. Curr Opin Immunol. 2011;23(6):702–6. https://doi.org/10.1016/j.coi.2011.08.007. Epub 2011/09/09. PubMed PMID: 21899997; PubMed Central PMCID: PMC3232281.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  231. Venken K, Hellings N, Thewissen M, Somers V, Hensen K, Rummens JL, et al. Compromised CD4+ CD25(high) regulatory T-cell function in patients with relapsing-remitting multiple sclerosis is correlated with a reduced frequency of FOXP3-positive cells and reduced FOXP3 expression at the single-cell level. Immunology. 2008;123(1):79–89. https://doi.org/10.1111/j.1365-2567.2007.02690.x. Epub 2007/09/28. PubMed PMID: 17897326; PubMed Central PMCID: PMC2433271.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  232. Huang YH, Zozulya AL, Weidenfeller C, Metz I, Buck D, Toyka KV, et al. Specific central nervous system recruitment of HLA-G(+) regulatory T cells in multiple sclerosis. Ann Neurol. 2009;66(2):171–83. https://doi.org/10.1002/ana.21705. Epub 2009/08/26. PubMed PMID: 19705413.

    Article  CAS  PubMed  Google Scholar 

  233. Frisullo G, Nociti V, Iorio R, Patanella AK, Caggiula M, Marti A, et al. Regulatory T cells fail to suppress CD4T+-bet+ T cells in relapsing multiple sclerosis patients. Immunology. 2009;127(3):418–28. https://doi.org/10.1111/j.1365-2567.2008.02963.x. Epub 2008/11/20. PubMed PMID: 19016907; PubMed Central PMCID: PMC2712110.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  234. Bailey-Bucktrout SL, Martinez-Llordella M, Zhou X, Anthony B, Rosenthal W, Luche H, et al. Self-antigen-driven activation induces instability of regulatory T cells during an inflammatory autoimmune response. Immunity. 2013;39(5):949–62. https://doi.org/10.1016/j.immuni.2013.10.016. PubMed PMID: 24238343; PubMed Central PMCID: PMC3912996.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  235. Ding X, Cao F, Cui L, Ciric B, Zhang GX, Rostami A. IL-9 signaling affects central nervous system resident cells during inflammatory stimuli. Exp Mol Pathol. 2015;99(3):570–4. https://doi.org/10.1016/j.yexmp.2015.07.010. Epub 2015/07/29. PubMed PMID: 26216406.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  236. Guo J, Zhao C, Wu F, Tao L, Zhang C, Zhao D, et al. T follicular helper-like cells are involved in the pathogenesis of experimental autoimmune encephalomyelitis. Front Immunol. 2018;9:944. https://doi.org/10.3389/fimmu.2018.00944. Epub 2018/06/06. PubMed PMID: 29867938; PubMed Central PMCID: PMCPMC5949363.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  237. Quinn JL, Kumar G, Agasing A, Ko RM, Axtell RC. Role of TFH cells in promoting T helper 17-induced neuroinflammation. Front Immunol. 2018;9:382. https://doi.org/10.3389/fimmu.2018.00382. Epub 2018/03/15. PubMed PMID: 29535739; PubMed Central PMCID: PMCPMC5835081.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  238. Dhaeze T, Peelen E, Hombrouck A, Peeters L, Van Wijmeersch B, Lemkens N, et al. Circulating follicular regulatory T cells are defective in multiple sclerosis. J Immunol. 2015;195(3):832–40. https://doi.org/10.4049/jimmunol.1500759. PubMed PMID: 26071562.

    Article  CAS  PubMed  Google Scholar 

  239. Liu C, Wang D, Song Y, Lu S, Zhao J, Wang H. Increased circulating CD4(+)CXCR5(+)FoxP3(+) follicular regulatory T cells correlated with severity of systemic lupus erythematosus patients. Int Immunopharmacol. 2018;56:261–8. https://doi.org/10.1016/j.intimp.2018.01.038. Epub 2018/02/08. PubMed PMID: 29414660.

    Article  CAS  PubMed  Google Scholar 

  240. Mayo L, Cunha AP, Madi A, Beynon V, Yang Z, Alvarez JI, et al. IL-10-dependent Tr1 cells attenuate astrocyte activation and ameliorate chronic central nervous system inflammation. Brain. 2016;139(Pt 7):1939–57. https://doi.org/10.1093/brain/aww113. PubMed PMID: 27246324; PubMed Central PMCID: PMCPMC4939696.

    Article  PubMed Central  PubMed  Google Scholar 

  241. Astier AL, Meiffren G, Freeman S, Hafler DA. Alterations in CD46-mediated Tr1 regulatory T cells in patients with multiple sclerosis. J Clin Invest. 2006;116(12):3252–7. https://doi.org/10.1172/JCI29251. Epub 2006/11/14. PubMed PMID: 17099776; PubMed Central PMCID: PMCPMC1635165.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  242. Wildbaum G, Netzer N, Karin N. Tr1 cell-dependent active tolerance blunts the pathogenic effects of determinant spreading. J Clin Invest. 2002;110(5):701–10. https://doi.org/10.1172/JCI15176. Epub 2002/09/05. PubMed PMID: 12208871; PubMed Central PMCID: PMCPMC151104.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  243. Chefdeville A, Honnorat J, Hampe CS, Desestret V. Neuronal central nervous system syndromes probably mediated by autoantibodies. Eur J Neurosci. 2016;43(12):1535–52. https://doi.org/10.1111/ejn.13212. Epub 2016/02/27. PubMed PMID: 26918657; PubMed Central PMCID: PMCPMC4914447.

    Article  PubMed Central  PubMed  Google Scholar 

  244. Fukuda T, Motomura M, Nakao Y, Shiraishi H, Yoshimura T, Iwanaga K, et al. Reduction of P/Q-type calcium channels in the postmortem cerebellum of paraneoplastic cerebellar degeneration with Lambert-Eaton myasthenic syndrome. Ann Neurol. 2003;53(1):21–8. https://doi.org/10.1002/ana.10392. Epub 2003/01/02. PubMed PMID: 12509844.

    Article  CAS  PubMed  Google Scholar 

  245. Kitanosono H, Shiraishi H, Motomura M. P/Q-type calcium channel antibodies in Lambert-Eaton Myasthenic Syndrome. Brain Nerve. 2018;70(4):341–55. https://doi.org/10.11477/mf.1416201007. Epub 2018/04/11. PubMed PMID: 29632282.

    Article  CAS  PubMed  Google Scholar 

  246. Graus F, Keime-Guibert F, Rene R, Benyahia B, Ribalta T, Ascaso C, et al. Anti-Hu-associated paraneoplastic encephalomyelitis: analysis of 200 patients. Brain J Neurol. 2001;124(Pt 6):1138–48. Epub 2001/05/17. PubMed PMID: 11353730.

    Article  CAS  Google Scholar 

  247. Peterson K, Rosenblum MK, Kotanides H, Posner JB. Paraneoplastic cerebellar degeneration. I. A clinical analysis of 55 anti-Yo antibody-positive patients. Neurology. 1992;42(10):1931–7. Epub 1992/10/01. PubMed PMID: 1407575.

    Article  CAS  PubMed  Google Scholar 

  248. Vernino S, Lennon VA. New Purkinje cell antibody (PCA-2): marker of lung cancer-related neurological autoimmunity. Ann Neurol. 2000;47(3):297–305. Epub 2000/03/15. PubMed PMID: 10716248.

    Article  CAS  PubMed  Google Scholar 

  249. Graus F, Dalmau J, Valldeoriola F, Ferrer I, Rene R, Marin C, et al. Immunological characterization of a neuronal antibody (anti-Tr) associated with paraneoplastic cerebellar degeneration and Hodgkin’s disease. J Neuroimmunol. 1997;74(1–2):55–61. Epub 1997/04/01. PubMed PMID: 9119979.

    Article  CAS  PubMed  Google Scholar 

  250. Yu Z, Kryzer TJ, Griesmann GE, Kim K, Benarroch EE, Lennon VA. CRMP-5 neuronal autoantibody: marker of lung cancer and thymoma-related autoimmunity. Ann Neurol. 2001;49(2):146–54. Epub 2001/02/28. PubMed PMID: 11220734.

    Article  CAS  PubMed  Google Scholar 

  251. Rosenfeld MR, Eichen JG, Wade DF, Posner JB, Dalmau J. Molecular and clinical diversity in paraneoplastic immunity to Ma proteins. Ann Neurol. 2001;50(3):339–48. Epub 2001/09/18. PubMed PMID: 11558790.

    Article  CAS  PubMed  Google Scholar 

  252. Perego L, Previtali SC, Nemni R, Longhi R, Carandente O, Saibene A, et al. Autoantibodies to amphiphysin I and amphiphysin II in a patient with sensory-motor neuropathy. Eur Neurol. 2002;47(4):196–200. https://doi.org/10.1159/000057898. Epub 2002/05/31. PubMed PMID: 12037431.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. National Centre for Cell Science, Pune, India

    Sandip Ashok Sonar & Girdhari Lal

Authors
  1. Sandip Ashok Sonar
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Girdhari Lal
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Girdhari Lal .

Editor information

Editors and Affiliations

  1. Medical Education Promotion Center, Tokyo Medical University, Tokyo, Japan

    Hiroshi Mitoma

  2. Department of Neurology, CHU-Charleroi, Charleroi, Belgium, Department of Neurosciences, University of Mons, Mons, Belgium

    Mario Manto

Rights and permissions

Reprints and permissions

Copyright information

© 2019 Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Sonar, S.A., Lal, G. (2019). Overview of Mechanisms Underlying Neuroimmune Diseases. In: Mitoma, H., Manto, M. (eds) Neuroimmune Diseases. Contemporary Clinical Neuroscience. Springer, Cham. https://doi.org/10.1007/978-3-030-19515-1_1

Download citation

Publish with us

Policies and ethics

Search

Navigation