Skip to main content

Advertisement

Log in

Lupus animal models and neuropsychiatric implications

  • Review Article
  • Published:
Clinical Rheumatology Aims and scope Submit manuscript

Abstract

Systemic lupus erythematosus (SLE) that involves neurological complications is known as neuropsychiatric systemic lupus erythematosus (NPSLE). Research in humans is difficult due to the disease’s great heterogeneity. Animal models are a resource for new discoveries. In this review, we examine experimental models of lupus that present neuropsychiatric manifestations. Spontaneous animal models such as NZB/W F1 and MRL/lpr are commonly used in NPSLE research; these models present few SLE symptoms compared to induced animal models, such as pristane-induced lupus (PIL). The PIL model is known to present eight of the main clinical and laboratory manifestations of SLE described by the American College of Rheumatology. Many cytokines associated with NPSLE are expressed in the PIL model, such as IL-6, TNF-α, and IFN. However, to date, NPSLE manifestations have been poorly studied in the PIL model. In this review article, we discuss whether the PIL model can mimic neuropsychiatric manifestations of SLE.

Key Points

• PIL model have a strong interferon signature.

• Animals with PIL express learning and memory deficit.

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

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Shaheen VM, Satoh M, Richards HB et al (1999) Immunopathogenesis of environmentally induced lupus in mice. Environ Health Perspect 107(Suppl):723–727. https://doi.org/10.1289/ehp.99107s5723

    Article  PubMed  PubMed Central  Google Scholar 

  2. Kivity S, Agmon-Levin N, Zandman-Goddard G et al (2015) Neuropsychiatric lupus: a mosaic of clinical presentations. BMC Med 13:43. https://doi.org/10.1186/s12916-015-0269-8

    Article  PubMed  PubMed Central  Google Scholar 

  3. Wen J, Stock AD, Chalmers SA, Putterman C (2016) The role of B cells and autoantibodies in neuropsychiatric lupus. Autoimmun Rev 15:890–895

    Article  CAS  Google Scholar 

  4. Aranow C, Diamond B, Mackay M (2012) Pathogenesis of the nervous system. In: Dubois’ lupus erythematosus and related syndromes: eighth edition. Pp 363–367

  5. Rizos T, Siegelin M, Hähnel S et al (2009) Fulminant onset of cerebral immunocomplex vasculitis as first manifestation of neuropsychiatric systemic lupus erythematosus (NPSLE). Lupus 18:361–363. https://doi.org/10.1177/0961203308097448

    Article  CAS  PubMed  Google Scholar 

  6. Vo A, Volpe BT, Tang CC et al (2014) Regional brain metabolism in a murine systemic lupus erythematosus model. J Cereb Blood Flow Metab 34:1315–1320. https://doi.org/10.1038/jcbfm.2014.85

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Kaul A, Gordon C, Crow MK et al (2016) Systemic lupus erythematosus. Nat Rev Dis Prim 2:16039. https://doi.org/10.1038/nrdp.2016.39

    Article  PubMed  Google Scholar 

  8. Shao W-H, Cohen PL (2011) Disturbances of apoptotic cell clearance in SLE. Arthritis Res Ther 13:202. https://doi.org/10.1186/ar3206

    Article  PubMed  PubMed Central  Google Scholar 

  9. Theofilopoulos AN, Kono DH, Beutler B, Baccala R (2011) Intracellular nucleic acid sensors and autoimmunity. J Interf Cytokine Res 31:867–886. https://doi.org/10.1089/jir.2011.0092

    Article  CAS  Google Scholar 

  10. Nelson P, Rylance P, Roden D et al (2014) Viruses as potential pathogenic agents in systemic lupus erythematosus. Lupus 23:596–605. https://doi.org/10.1177/0961203314531637

    Article  CAS  PubMed  Google Scholar 

  11. Wolf SJ, Estadt SN, Theros J et al (2019) Ultraviolet light induces increased T cell activation in lupus-prone mice via type I IFN-dependent inhibition of T regulatory cells. J Autoimmun 103:102291. https://doi.org/10.1016/j.jaut.2019.06.002

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Parks CG, de Souza Espindola Santos A, Barbhaiya M, Costenbader KH (2017) Understanding the role of environmental factors in the development of systemic lupus erythematosus. Best Pract Res Clin Rheumatol 31:306–320. https://doi.org/10.1016/j.berh.2017.09.005

    Article  PubMed  PubMed Central  Google Scholar 

  13. Yap DYH, Lai KN (2010) Cytokines and their roles in the pathogenesis of systemic lupus erythematosus: from basics to recent advances. J Biomed Biotechnol 2010:365083. https://doi.org/10.1155/2010/365083

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Sule S, Rosen A, Petri M et al (2011) Abnormal production of pro- and anti-inflammatory cytokines by lupus monocytes in response to apoptotic cells. PLoS One 6:e17495. https://doi.org/10.1371/journal.pone.0017495

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Baechler EC, Batliwalla FM, Karypis G et al (2003) Interferon-inducible gene expression signature in peripheral blood cells of patients with severe lupus. Proc Natl Acad Sci U S A 100:2610–2615. https://doi.org/10.1073/pnas.0337679100

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Dall’Era MC, Cardarelli PM, Preston BT et al (2005) Type I interferon correlates with serological and clinical manifestations of SLE. Ann Rheum Dis 64:1692–1697. https://doi.org/10.1136/ard.2004.033753

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Pieterse E, van der Vlag J (2014) Breaking immunological tolerance in systemic lupus erythematosus. Front Immunol 5. https://doi.org/10.3389/fimmu.2014.00164

  18. Ginzler E, Tayar J (2013) Systemic lupus erythematosus. Am Coll Rheumatol:1–6. https://doi.org/10.1007/SpringerReference_61618

  19. Bertsias GK, Ioannidis JPA, Aringer M et al (2010) EULAR recommendations for the management of systemic lupus erythematosus with neuropsychiatric manifestations: report of a task force of the EULAR standing committee for clinical affairs. Ann Rheum Dis 69:2074–2082. https://doi.org/10.1136/ard.2010.130476

    Article  CAS  PubMed  Google Scholar 

  20. Liang MH, Corzillius M, Bae SC et al (1999) The American College of Rheumatology nomenclature and case definitions for neuropsychiatric lupus syndromes. Arthritis Rheum 42:599–608. https://doi.org/10.1002/1529-0131(199904)42:4<599::AID-ANR2>3.0.CO;2-F

    Article  Google Scholar 

  21. Lacomis D, Živković SA (2007) Approach to vasculitic neuropathies. J Clin Neuromuscul Dis 9:265–276

    Article  Google Scholar 

  22. Sciascia S, Bertolaccini ML, Roccatello D et al (2014) Autoantibodies involved in neuropsychiatric manifestations associated with systemic lupus erythematosus: a systematic review. J Neurol 261:1706–1714. https://doi.org/10.1007/s00415-014-7406-8

    Article  CAS  PubMed  Google Scholar 

  23. Wallace DJ, Hahn BH (2018) Dubois’ lupus erythematosus and related syndromes

  24. Hanly JG (2014) Diagnosis and management of neuropsychiatric SLE. Nat. Rev. Rheumatol

  25. Stock AD, Wen J, Putterman C (2013) Neuropsychiatric lupus, the blood brain barrier, and the TWEAK/Fn14 pathway. Front Immunol 4. https://doi.org/10.3389/fimmu.2013.00484

  26. Ballok DA, Millward JM, Sakic B (2003) Neurodegeneration in autoimmune MRL-lpr mice as revealed by Fluoro Jade B staining. Brain Res. https://doi.org/10.1016/S0006-8993(02)03980-X

  27. De Boer AG, Gaillard PJ (2006) Blood-brain barrier dysfunction and recovery. J Neural Transm 113:455–462. https://doi.org/10.1007/s00702-005-0375-4

    Article  PubMed  Google Scholar 

  28. Sharif Y, Jumah F, Coplan L et al (2018) Blood brain barrier: a review of its anatomy and physiology in health and disease. Clin Anat 31:812–823. https://doi.org/10.1002/ca.23083

    Article  PubMed  Google Scholar 

  29. Bonkowski D, Katyshev V, Balabanov RD, et al (2011) The CNS microvascular pericyte: pericyte-astrocyte crosstalk in the regulation of tissue survival. Fluids Barriers CNS 8

  30. Patel JP, Frey BN (2015) Disruption in the blood-brain barrier: the missing link between brain and body inflammation in bipolar disorder? Neural Plast 2015

  31. Jacob A, Hack B, Chen P et al (2011) C5a/CD88 signaling alters blood-brain barrier integrity in lupus through nuclear factor-κB. J Neurochem 119:1041–1051. https://doi.org/10.1111/j.1471-4159.2011.07490.x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Jafri K, Patterson SL, Lanata C (2017) Central nervous system manifestations of systemic lupus erythematosus. Rheum Dis Clin N Am 43:531–545. https://doi.org/10.1016/j.rdc.2017.06.003

    Article  Google Scholar 

  33. Kowal C, DeGiorgio LA, Lee JY et al (2006) Human lupus autoantibodies against NMDA receptors mediate cognitive impairment. Proc Natl Acad Sci 103:19854–19859. https://doi.org/10.1073/pnas.0608397104

    Article  CAS  PubMed  Google Scholar 

  34. Gelb S, Stock AD, Anzi S et al (2018) Mechanisms of neuropsychiatric lupus: the relative roles of the blood-cerebrospinal fluid barrier versus blood-brain barrier. J Autoimmun 91:34–44. https://doi.org/10.1016/j.jaut.2018.03.001

    Article  PubMed  PubMed Central  Google Scholar 

  35. Gelb S, Stock AD, Anzi S et al (2018) Mechanisms of neuropsychiatric lupus: the relative roles of the blood-CSF versus blood-brain barrier HHS public access. J Autoimmun 91:34–44. https://doi.org/10.1016/j.jaut.2018.03.001

    Article  PubMed  PubMed Central  Google Scholar 

  36. Blank T, Prinz M (2017) Type I interferon pathway in CNS homeostasis and neurological disorders. Glia 65:1397–1406. https://doi.org/10.1002/glia.23154

    Article  PubMed  Google Scholar 

  37. Rice GI, Rodero MP, Crow YJ (2015) Human disease phenotypes associated with mutations in TREX1. J Clin Immunol 35:235–243. https://doi.org/10.1007/s10875-015-0147-3

    Article  CAS  Google Scholar 

  38. Kisla Ekinci RM, Balci S, Bisgin A et al (2017) A homozygote TREX1 mutation in two siblings with different phenotypes: chilblains and cerebral vasculitis. Eur J Med Genet 60:690–694. https://doi.org/10.1016/j.ejmg.2017.09.004

    Article  PubMed  Google Scholar 

  39. Appenzeller S, Costallat LTL (2007) Central nervous system manifestations in systemic lupus erythematosus. Curr Rheumatol Rev 3:205–214. https://doi.org/10.2174/157339707781387572

    Article  Google Scholar 

  40. Lipsky PE (2001) Systemic lupus erythematosus: an autoimmune disease of B cell hyperactivity. Nat Immunol 2:764–766. https://doi.org/10.1038/ni0901-764

    Article  CAS  PubMed  Google Scholar 

  41. Perry D, Sang A, Yin Y et al (2011) Murine models of systemic lupus erythematosus. J Biomed Biotechnol 2011:1–19. https://doi.org/10.1155/2011/271694

    Article  Google Scholar 

  42. Richard ML, Gilkeson G (2018) Mouse models of lupus: what they tell us and what they don’t. Lupus Sci Med 5:e000199. https://doi.org/10.1136/lupus-2016-000199

    Article  PubMed  PubMed Central  Google Scholar 

  43. Theofilopoulos AN, Dixon FJ (1985) Murine models of systemic lupus erythematosus. Adv Immunol 269–390:v9

    Google Scholar 

  44. Jeltsch-David H, Muller S (2014) Neuropsychiatric systemic lupus erythematosus: pathogenesis and biomarkers. Nat Rev Neurol 10:579–596. https://doi.org/10.1038/nrneurol.2014.148

    Article  CAS  PubMed  Google Scholar 

  45. Andrews BS, Eisenberg RA, Theofilopoulos AN et al (1978) Spontaneous murine lupus-like syndromes: clinical and immunopathological manifestations in several strains*. J Exp Med 148:1198–1215. https://doi.org/10.1084/jem.148.5.1198

    Article  CAS  PubMed  Google Scholar 

  46. Freitas EC, de Oliveira MS, Monticielo OA (2017) Pristane-induced lupus: considerations on this experimental model. Clin Rheumatol 36:2403–2414. https://doi.org/10.1007/s10067-017-3811-6

    Article  PubMed  Google Scholar 

  47. Luciano-Jaramillo J, Sandoval-García F, Vázquez-Del Mercado M et al (2019) Downregulation of hippocampal NR2A/2B subunits related to cognitive impairment in a pristane-induced lupus BALB/c mice. PLoS One 14:e0217190. https://doi.org/10.1371/journal.pone.0217190

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Nacionales DC, Kelly-Scumpia KM, Lee PY et al (2007) Deficiency of the type I interferon receptor protects mice from experimental lupus. Arthritis Rheum 56:3770–3783. https://doi.org/10.1002/art.23023

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Correa Freitas E, Evelyn Karnopp T, de Souza Silva JM et al (2019) Vitamin D supplementation ameliorates arthritis but does not alleviates renal injury in pristane-induced lupus model. Autoimmunity 52:69–77. https://doi.org/10.1080/08916934.2019.1613383

    Article  CAS  PubMed  Google Scholar 

  50. Kier AB (1990) Clinical neurology and brain histopathology in NZB/NZW F1 lupus mice. J Comp Pathol 102:165–177. https://doi.org/10.1016/S0021-9975(08)80122-3

    Article  CAS  PubMed  Google Scholar 

  51. Gao HX, Campbell SR, Cui MH et al (2009) Depression is an early disease manifestation in lupus-prone MRL/lpr mice. J Neuroimmunol. https://doi.org/10.1016/j.jneuroim.2008.11.009

  52. Gulinello M, Putterman C (2011) The MRL/lpr mouse strain as a model for neuropsychiatric systemic lupus erythematosus. J Biomed Biotechnol 2011:1–15. https://doi.org/10.1155/2011/207504

    Article  Google Scholar 

  53. Šakić B, Szechtman H, Talangbayan H et al (1994) Disturbed emotionality in autoimmune MRL-lpr mice. Physiol Behav 56:609–617. https://doi.org/10.1016/0031-9384(94)90309-3

    Article  PubMed  Google Scholar 

  54. He Y-YY, Yan YY, Zhang H-FF et al (2016) Methyl salicylate 2-O-β-D-lactoside alleviates the pathological progression of pristane-induced systemic lupus erythematosus-like disease in mice via suppression of inflammatory response and signal transduction. Drug Des Devel Ther Volume 10:3183–3196. https://doi.org/10.2147/DDDT.S114501

    Article  CAS  Google Scholar 

  55. Wu WM, Lin BF, Su YC et al (2000) Tamoxifen decreases renal inflammation and alleviates disease severity autoimmune NZB/W F1 mice. Scand J Immunol 52:393–400. https://doi.org/10.1046/j.1365-3083.2000.00789.x

    Article  CAS  PubMed  Google Scholar 

  56. Zhuang H, Szeto C, Han S et al (2015) Animal models of interferon signature positive lupus. Front Immunol 6. https://doi.org/10.3389/fimmu.2015.00291

  57. Tang B, Matsuda T, Akira S et al (1991) Age-associated increase in interleukin 6 in MRL/lpr mice. Int Immunol 3:273–278

    Article  CAS  Google Scholar 

  58. Tsai C-Y, Wu T-H, Huang S-F et al (1995) Abnormal splenic and thymic IL-4 and TNF-α expression in MRL-lpr/lpr mice. Scand J Immunol 41:157–163. https://doi.org/10.1111/j.1365-3083.1995.tb03548.x

    Article  CAS  PubMed  Google Scholar 

  59. Li P, Lin W, Zheng X (2014) IL-33 neutralization suppresses lupus disease in lupus-prone mice. Inflammation 37:824–832. https://doi.org/10.1007/s10753-013-9802-0

    Article  CAS  PubMed  Google Scholar 

  60. Murphy ED, Roths JB (1979) A y chromosome associated factor in strain bxsb producing accelerated autoimmunity and lymphoproliferation. Arthritis Rheum 22:1188–1194. https://doi.org/10.1002/art.1780221105

    Article  CAS  PubMed  Google Scholar 

  61. Satoh M (1994) Induction of lupus-associated autoantibodies in BALB/c mice by intraperitoneal injection of pristane. J Exp Med 180:2341–2346. https://doi.org/10.1084/jem.180.6.2341

    Article  CAS  PubMed  Google Scholar 

  62. Satoh M, Kumar A, Kanwar YS, Reeves WH (1995) Anti-nuclear antibody production and immune-complex glomerulonephritis in BALB/c mice treated with pristane. Proc Natl Acad Sci U S A 92:10934–10938. https://doi.org/10.1073/pnas.92.24.10934

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Satoh M, Hamilton KJ, Ajmani AK et al (1996) Autoantibodies to ribosomal P antigens with immune complex glomerulonephritis in SJL mice treated with pristane. J Immunol 157:3200–3206

    CAS  PubMed  Google Scholar 

  64. Satoh M, Richards HB, Shaheen VM et al (2000) Widespread susceptibility among inbred mouse strains to the induction of lupus autoantibodies by pristane. Clin Exp Immunol 121:399–405. https://doi.org/10.1046/j.1365-2249.2000.01276.x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Richards HB (2002) Interleukin 6 dependence of anti-DNA antibody production: evidence for two pathways of autoantibody formation in pristane-induced lupus. J Exp Med 188:985–990. https://doi.org/10.1084/jem.188.5.985

    Article  Google Scholar 

  66. Reeves WH, Lee PY, Weinstein JS et al (2009) Induction of autoimmunity by pristane and other naturally occurring hydrocarbons. Trends Immunol 30:455–464. https://doi.org/10.1016/j.it.2009.06.003

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Kalim H, Pratama MZ, Nugraha AS et al (2018) Regulatory T cells compensation failure cause the dysregulation of immune response in pristane induced lupus mice model. Malays J Med Sci 25:17–26. https://doi.org/10.21315/mjms2018.25.3.3

    Article  PubMed  PubMed Central  Google Scholar 

  68. Schwartz N, Stock AD, Putterman C (2019) Neuropsychiatric lupus: new mechanistic insights and future treatment directions. Nat Rev Rheumatol 15:137–152

    Article  Google Scholar 

  69. Bortoluzzi A, Piga M, Silvagni E et al (2019) Peripheral nervous system involvement in systemic lupus erythematosus: a retrospective study on prevalence, associated factors and outcome. Lupus 28:465–474. https://doi.org/10.1177/0961203319828499

    Article  CAS  PubMed  Google Scholar 

  70. Bendorius M, Po C, Muller S, Jeltsch-David H (2018) From systemic inflammation to neuroinflammation: the case of neurolupus. Int J Mol Sci 19:3588. https://doi.org/10.3390/ijms19113588

    Article  CAS  PubMed Central  Google Scholar 

  71. Helyer BJ, Howie JB (1963) Renal disease associated with positive lupus erythematosus tests in a crossbred strain of mice. Nature. https://doi.org/10.1038/197197a0

  72. Drake CG, Rozzo SJ, Hirschfeld HF et al (1995) Analysis of the New Zealand Black contribution to lupus-like renal disease. Multiple genes that operate in a threshold manner. J Immunol 54:2441–2447

    Google Scholar 

  73. Bracci-Laudiero L, Aloe L, Lundeberg T, et al (1999) Altered levels of neuropeptides characterize the brain of lupus prone mice. Neurosci Lett

  74. Ballok DA (2007) Neuroimmunopathology in a murine model of neuropsychiatric lupus. Brain Res Rev 54:67–79. https://doi.org/10.1016/j.brainresrev.2006.12.003

    Article  CAS  PubMed  Google Scholar 

  75. Murphy ED, Roths JB (1979) A y chromosome associated factor in strain bxsb producing accelerated autoimmunity and lymphoproliferation. Arthritis Rheum https://doi.org/10.1002/art.1780221105

  76. Li Y, Eskelund AR, Zhou H et al (2015) Behavioral deficits are accompanied by immunological and neurochemical changes in a mouse model for neuropsychiatric lupus (NP-SLE). Int J Mol Sci 16:15150–15171. https://doi.org/10.3390/ijms160715150

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Ballok DA, Woulfe J, Sur M et al (2004) Hippocampal damage in mouse and human forms of systemic autoimmune disease. Hippocampus 14:649–661

    Article  Google Scholar 

  78. Gilkeson GS (2015) Complement-targeted therapies in lupus. Curr Treat Options Rheumatol 1:10–18. https://doi.org/10.1007/s40674-014-0009-9

    Article  Google Scholar 

  79. Alexander JJ, Bao L, Jacob A et al (2003) Administration of the soluble complement inhibitor, Crry-Ig, reduces inflammation and aquaporin 4 expression in lupus cerebritis. Biochim Biophys Acta Mol basis Dis 1639:169–176. https://doi.org/10.1016/j.bbadis.2003.09.005

    Article  CAS  Google Scholar 

  80. Ma X, Foster J, Sakic B (2006) Distribution and prevalence of leukocyte phenotypes in brains of lupus-prone mice. J Neuroimmunol 179:26–36. https://doi.org/10.1016/j.jneuroim.2006.06.023

    Article  CAS  PubMed  Google Scholar 

  81. Mike EV, Makinde HM, Der E et al (2018) Neuropsychiatric systemic lupus erythematosus is dependent on sphingosine-1-phosphate signaling. Front Immunol 9:2189. https://doi.org/10.3389/fimmu.2018.02189

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Dean GS (2000) Cytokines and systemic lupus erythematosus. Ann Rheum Dis 59:243–251. https://doi.org/10.1136/ard.59.4.243

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Arisi GM (2014) Nervous and immune systems signals and connections: cytokines in hippocampus physiology and pathology. Epilepsy Behav 38:43–47

    Article  Google Scholar 

  84. Dinan TG, Dinan T (2009) Inflammatory markers in depression. Curr Opin Psychiatry 22:32–36

    Article  Google Scholar 

  85. Tomita M, Khan RL, Blehm BH, Santoro TJ (2004) The potential pathogenetic link between peripheral immune activation and the central innate immune response in neuropsychiatric systemic lupus erythematosus. Med Hypotheses 62:325–335. https://doi.org/10.1016/j.mehy.2003.10.009

    Article  CAS  PubMed  Google Scholar 

  86. Han J-HH, Umiker BR, Kazimirova AA et al (2014) Expression of an anti-RNA autoantibody in a mouse model of SLE increases neutrophil and monocyte numbers as well as IFN-I expression. Eur J Immunol 44:215–226. https://doi.org/10.1002/eji.201343714

    Article  CAS  PubMed  Google Scholar 

  87. Shi D, Tian T, Yao S et al (2018) FTY720 attenuates behavioral deficits in a murine model of systemic lupus erythematosus. Brain Behav Immun 70:293–304. https://doi.org/10.1016/j.bbi.2018.03.009

    Article  CAS  PubMed  Google Scholar 

  88. Mike EV, Makinde HM, Gulinello M et al (2019) Lipocalin-2 is a pathogenic determinant and biomarker of neuropsychiatric lupus. J Autoimmun 96:59–73. https://doi.org/10.1016/j.jaut.2018.08.005

    Article  CAS  PubMed  Google Scholar 

  89. Cuda CM, Misharin AV, Gierut AK et al (2014) Caspase-8 acts as a molecular rheostat to limit RIPK1- and MyD88-mediated dendritic cell activation. J Immunol 192:5548–5560. https://doi.org/10.4049/jimmunol.1400122

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Makinde HM, Winter DR, Procissi D et al (2020) A novel microglia-specific transcriptional signature correlates with behavioral deficits in neuropsychiatric lupus. Front Immunol 11. https://doi.org/10.3389/fimmu.2020.00230

  91. Nacionales DC, Kelly KM, Lee PY et al (2006) Type I interferon production by tertiary lymphoid tissue developing in response to 2,6,10,14-tetramethyl-pentadecane (pristane). Am J Pathol 168:1227–1240. https://doi.org/10.2353/ajpath.2006.050125

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Alexander JJ, Jacob A, Bao L et al (2005) Complement-dependent apoptosis and inflammatory gene changes in murine lupus cerebritis. J Immunol 175:8312–8319. https://doi.org/10.4049/jimmunol.175.12.8312

    Article  CAS  PubMed  Google Scholar 

  93. Lee PY, Weinstein JS, Nacionales DC et al (2014) A novel type I IFN-producing cell subset in murine lupus. J Immunol 180:5101–5108. https://doi.org/10.4049/jimmunol.180.7.5101

    Article  Google Scholar 

  94. Tomita M, Holman BJ, Santoro TJ (2001) Aberrant cytokine gene expression in the hippocampus in murine systemic lupus erythematosus. Neurosci Lett 302:129–132. https://doi.org/10.1016/S0304-3940(01)01679-2

    Article  CAS  PubMed  Google Scholar 

  95. Tomita M, Holman BJ, Williams LS et al (2001) Cerebellar dysfunction is associated with overexpression of proinflammatory cytokine genes in lupus. J Neurosci Res 64:26–33. https://doi.org/10.1002/jnr.1050

    Article  CAS  PubMed  Google Scholar 

  96. Jeltsch-David H, Muller S (2014) Neuropsychiatric systemic lupus erythematosus and cognitive dysfunction: the MRL-lpr mouse strain as a model. Autoimmun Rev 13:963–973. https://doi.org/10.1016/j.autrev.2014.08.015

    Article  PubMed  Google Scholar 

  97. Murphy E, Roths J (1978) Autoimmunity and lymphoproliferation. Induction by mutant gene lpr, and acceleration by a male-associated factor in strain BXSB mice. In: Rose N, Bigazzi P, Warner N (eds) Genetic control of autoimmune disease. Elsevier, New York, pp 207–221

    Google Scholar 

  98. Furukawa F, Hamashima Y (1982) Lupus band test in New Zealand mice and MRL mice. J Dermatol 9:467–471. https://doi.org/10.1111/j.1346-8138.1982.tb01091.x

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

We acknowledge the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), Brazil, for a scholarship offered to Thaís Evelyn Karnopp and the Pró-Reitoria de Pesquisa (PROPESQ) of the Universidade Federal do Rio Grande do Sul (UFRGS), Brazil, for a scholarship offered to Gustavo Flores Chapacais.

Funding

This study was supported by the Research Incentive Fund (FIPE/HCPA: grant no. 18-0246), Conselho Nacional de Desenvolvimento Cientıfico e Tecnologico Universal (MCTI/CNPQ: grant no. 28/2018), and the Research Support Fund of the Sociedade de Reumatologia do Rio Grande do Sul.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Thaís Evelyn Karnopp.

Ethics declarations

Disclosures

None.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Karnopp, T.E., Chapacais, G.F., Freitas, E.C. et al. Lupus animal models and neuropsychiatric implications. Clin Rheumatol 40, 2535–2545 (2021). https://doi.org/10.1007/s10067-020-05493-7

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10067-020-05493-7

Keywords

Navigation