Acta Neuropathologica

, Volume 132, Issue 3, pp 391–411 | Cite as

Peripheral monocytes are functionally altered and invade the CNS in ALS patients

  • Lisa Zondler
  • Kathrin Müller
  • Samira Khalaji
  • Corinna Bliederhäuser
  • Wolfgang P. Ruf
  • Veselin Grozdanov
  • Meinolf Thiemann
  • Katrin Fundel-Clemes
  • Axel Freischmidt
  • Karlheinz Holzmann
  • Benjamin Strobel
  • Patrick Weydt
  • Anke Witting
  • Dietmar R. Thal
  • Anika M. Helferich
  • Bastian Hengerer
  • Kay-Eberhard Gottschalk
  • Oliver Hill
  • Michael Kluge
  • Albert C. Ludolph
  • Karin M. Danzer
  • Jochen H. Weishaupt
Original Paper


Amyotrophic lateral sclerosis (ALS) is a devastating progressive neurodegenerative disease affecting primarily the upper and lower motor neurons. A common feature of all ALS cases is a well-characterized neuroinflammatory reaction within the central nervous system (CNS). However, much less is known about the role of the peripheral immune system and its interplay with CNS resident immune cells in motor neuron degeneration. Here, we characterized peripheral monocytes in both temporal and spatial dimensions of ALS pathogenesis. We found the circulating monocytes to be deregulated in ALS regarding subtype constitution, function and gene expression. Moreover, we show that CNS infiltration of peripheral monocytes correlates with improved motor neuron survival in a genetic ALS mouse model. Furthermore, application of human immunoglobulins or fusion proteins containing only the human Fc, but not the Fab antibody fragment, increased CNS invasion of peripheral monocytes and delayed the disease onset. Our results underline the importance of peripheral monocytes in ALS pathogenesis and are in agreement with a protective role of monocytes in the early phase of the disease. The possibility to boost this beneficial function of peripheral monocytes by application of human immunoglobulins should be evaluated in clinical trials.


Amyotrophic lateral sclerosis Monocyte Innate immunity Microglia Immunoglobulin Fc receptor 



We thank all blood donors, healthy control probands, as well as ALS patients and pre-symptomatic mutation carriers for participation in this study. We thank all physicians at the neurologic university clinic Ulm for recruiting and taking care of the patients who have participated in this study. We thank Antje Knehr for organizing the collection of blood from members of ALS families and we thank Birgit Linkus, Tanja Wipp, Diana Wiesner, Nadine Todt, Elena Jasovskaja, Johannes Hanselmann, and Eva Barth for technical assistance. This research was supported by the Thierry Latran Foundation.

Compliance with ethical standards


This work has been funded by the Thierry Latran Foundation, Grant Number: FTLAAP213/Weishaupt/innatetarget.

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional research committee (Ethics Committee of Ulm University) and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. Informed written consent was obtained from all individual participants included in the study prior to inclusion. All applicable international, national, and institutional guidelines for the care and use of animals were followed. All procedures performed in studies involving animals were in accordance with the ethical standards of the institution or practice at which the studies were conducted. All animal procedures were approved by the Regierungspräsidium Baden-Württemberg, Tübingen, Germany (No. 1090), and conducted according to the guidelines of the German Tierschutzgesetz.

Supplementary material

401_2016_1548_MOESM1_ESM.pdf (1.7 mb)
Supplementary material 1 (PDF 1713 kb)


  1. 1.
    Ahmed Z, Shaw G, Sharma VP, Yang C, McGowan E, Dickson DW (2007) Actin-binding proteins coronin-1a and IBA-1 are effective microglial markers for immunohistochemistry. J Histochem Cytochem 55:687–700. doi: 10.1369/jhc.6A7156.2007 CrossRefPubMedGoogle Scholar
  2. 2.
    Ajami B, Bennett JL, Krieger C, Tetzlaff W, Rossi FMV (2007) Local self-renewal can sustain CNS microglia maintenance and function throughout adult life. Nat Neurosci 10: 1538–1543. Accessed 19 Nov 2015
  3. 3.
    Appel SH, Zhao W, Beers DR, Henkel JS (2011) The microglial-motoneuron dialogue in ALS. Acta Myologica 30:4–8PubMedPubMedCentralGoogle Scholar
  4. 4.
    Beers DR, Henkel JS, Zhao W, Wang J, Appel SH (2008) CD4+ T cells support glial neuroprotection, slow disease progression, and modify glial morphology in an animal model of inherited ALS. Proc Natl Acad Sci USA 105:15558–15563. doi: 10.1073/pnas.0807419105 CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Boillée S, Yamanaka K, Lobsiger CS, Copeland NG, Jenkins NA, Kassiotis G et al (2006) Onset and progression in inherited ALS determined by motor neurons and microglia. Science 312:1389–1392. doi: 10.1126/science.1123511 CrossRefPubMedGoogle Scholar
  6. 6.
    Bradley WG (2009) Updates on amyotrophic lateral sclerosis: improving patient care. Ann Neurol 65:S1–S2. doi: 10.1002/ana.21546 CrossRefPubMedGoogle Scholar
  7. 7.
    Brettschneider J, Libon DJ, Toledo JB, Xie SX, McCluskey L, Elman L et al (2012) Microglial activation and TDP-43 pathology correlate with executive dysfunction in amyotrophic lateral sclerosis. Acta Neuropathol 123:395–407. doi: 10.1007/s00401-011-0932-x CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Brettschneider J, Toledo JB, Van Deerlin VM, Elman L, McCluskey L, Lee VMY et al (2012) Microglial activation correlates with disease progression and upper motor neuron clinical symptoms in amyotrophic lateral sclerosis. PLoS One 7:e39216. doi: 10.1371/journal.pone.0039216 CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Bruhns P (2012) Properties of mouse and human IgG receptors and their contribution to disease models. Blood 119(24):5640–5649. doi: 10.1182/blood-2012-01-380121 CrossRefPubMedGoogle Scholar
  10. 10.
    Butovsky O, Siddiqui S, Gabriely G, Lanser AJ, Dake B, Murugaiyan G et al (2012) Modulating inflammatory monocytes with a unique microRNA gene signature ameliorates murine ALS. J Clin Invest 122:3063–3087. doi: 10.1172/JCI62636 CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Butovsky O, Jedrychowski MP, Moore CS, Cialic R, Lanser AJ, Gabriely G et al (2014) Identification of a unique TGF-β dependent molecular and functional signature in microglia. Nat Neurosci 17:131–143. doi: 10.1038/nn.3599 CrossRefPubMedGoogle Scholar
  12. 12.
    Butovsky O, Jedrychowski MP, Cialic R, Krasemann S, Murugaiyan G, Fanek Z et al (2015) Targeting miR-155 restores abnormal microglia and attenuates disease in SOD1 mice. Ann Neurol 77:75–99. doi: 10.1002/ana.24304 CrossRefPubMedGoogle Scholar
  13. 13.
    Chiu IM, Phatnani H, Kuligowski M, Tapia JC, Carrasco MA, Zhang M et al (2009) Activation of innate and humoral immunity in the peripheral nervous system of ALS transgenic mice. Proc Natl Acad Sci USA 106:20960–20965. doi: 10.1073/pnas.0911405106 CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Chiu IM, Morimoto ETA, Goodarzi H, Liao JT, O’Keeffe S, Phatnani HP et al (2013) A Neurodegeneration-specific gene-expression signature of acutely isolated microglia from an amyotrophic lateral sclerosis mouse model. Cell Reports 4:385–401. doi: 10.1016/j.celrep.2013.06.018 CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Clay CC, Rodrigues DS, Ho YS, Fallert BA, Janatpour K, Reinhart TA et al (2007) Neuroinvasion of fluorescein-positive monocytes in acute simian immunodeficiency virus infection. J Virol 81:12040–12048. doi: 10.1128/jvi.00133-07 CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Cleveland DW, Rothstein JD (2001) From charcot to lou gehrig: deciphering selective motor neuron death in als. Nat Rev Neurosci 2:806–819CrossRefPubMedGoogle Scholar
  17. 17.
    Cros J, Cagnard N, Woollard K, Patey N, Zhang SY, Senechal B et al (2010) Human CD14dim monocytes patrol and sense nucleic acids and viruses via TLR7 and TLR8 receptors. Immunity 33:375–386. doi: 10.1016/j.immuni.2010.08.012 CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    D’Mello C, Le T, Swain MG (2009) Cerebral microglia recruit monocytes into the brain in response to tumor necrosis factorα signaling during peripheral organ inflammation. J Neurosci 29:2089–2102. doi: 10.1523/jneurosci.3567-08.2009 CrossRefPubMedGoogle Scholar
  19. 19.
    Das A, Sinha M, Datta S, Abas M, Chaffee S, Sen CK et al. (2015) Monocyte and macrophage plasticity in tissue repair and regeneration. Am J Pathol. 185(10):2596–2606. doi:  10.1016/j.ajpath.2015.06.001 CrossRefPubMedGoogle Scholar
  20. 20.
    Davies LC, Jenkins SJ, Allen JE, Taylor PR (2013) Tissue-resident macrophages. Nat Immunol 14:986–995. doi: 10.1038/ni.2705 CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    DeJesus-Hernandez M, Mackenzie IR, Boeve BF, Boxer AL, Baker M, Rutherford NJ et al (2011) Expanded GGGGCC hexanucleotide repeat in non-coding region of C9ORF72 causes chromosome 9p-linked frontotemporal dementia and amyotrophic lateral sclerosis. Neuron 72:245–256. doi: 10.1016/j.neuron.2011.09.011 CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Delneste Y, Charbonnier P, Herbault N, Magistrelli G, Caron G, Bonnefoy JY et al (2003) Interferon-γ switches monocyte differentiation from dendritic cells to macrophages. Blood 101:143–150. doi: 10.1182/blood-2002-04-1164 CrossRefPubMedGoogle Scholar
  23. 23.
    Freischmidt A, Müller K, Zondler L, Weydt P, Mayer B, von Arnim CAF et al (2015) Serum microRNAs in sporadic amyotrophic lateral sclerosis. Neurobiol Aging 36(9):2660.e15–20. doi:  10.1016/j.neurobiolaging.2015.06.003 CrossRefPubMedGoogle Scholar
  24. 24.
    Freischmidt A, Müller K, Zondler L, Weydt P, Volk AE, Božič AL et al (2014) Serum microRNAs in patients with genetic amyotrophic lateral sclerosis and pre-manifest mutation carriers. Brain pp 2938–2950. doi: 10.1093/brain/awu249
  25. 25.
    Gao L, Brenner D, Llorens-Bobadilla E, Saiz-Castro G, Frank T, Wieghofer P et al (2015) Infiltration of circulating myeloid cells through CD95L contributes to neurodegeneration in mice. J Exp Med 212:469–480. doi: 10.1084/jem.20132423 CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Ginhoux F, Jung S (2014) Monocytes and macrophages: developmental pathways and tissue homeostasis. Nat Rev Immunol 14:392–404. doi: 10.1038/nri3671 CrossRefPubMedGoogle Scholar
  27. 27.
    Graber DJ, Hickey WF, Harris BT (2010) Progressive changes in microglia and macrophages in spinal cord and peripheral nerve in the transgenic rat model of amyotrophic lateral sclerosis. J Neuroinflammation 7:8. doi: 10.1186/1742-2094-7-8 CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Grozdanov V, Bliederhaeuser C, Ruf WP, Roth V, Fundel-Clemens K, Zondler L et al (2014) Inflammatory dysregulation of blood monocytes in Parkinson’s disease patients. Acta Neuropathol 128:651–663. doi: 10.1007/s00401-014-1345-4 CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    Gruzman A, Wood WL, Alpert E, Prasad MD, Miller RG, Rothstein JD et al (2007) Common molecular signature in SOD1 for both sporadic and familial amyotrophic lateral sclerosis. Proc Natl Acad Sci USA 104:12524–12529. doi: 10.1073/pnas.0705044104 CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    Gurney M, Pu H, Chiu A, Dal Canto M, Polchow C, Alexander D et al (1994) Motor neuron degeneration in mice that express a human Cu, Zn superoxide dismutase mutation. Science 264:1772–1775. doi: 10.1126/science.8209258 CrossRefPubMedGoogle Scholar
  31. 31.
    Henkel JS, Engelhardt JI, Siklós L, Simpson EP, Kim SH, Pan T et al (2004) Presence of dendritic cells, MCP-1, and activated microglia/macrophages in amyotrophic lateral sclerosis spinal cord tissue. Ann Neurol 55:221–235. doi: 10.1002/ana.10805 CrossRefPubMedGoogle Scholar
  32. 32.
    Hohsfield LA, Humpel C (2015) Migration of blood cells to β-amyloid plaques in Alzheimer’s disease. Exp Gerontol 65:8–15. doi: 10.1016/j.exger.2015.03.002 CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    Hübers A, Marroquin N, Schmoll B, Vielhaber S, Just M, Mayer B et al (2014) Polymerase chain reaction and Southern blot-based analysis of the C9orf72 hexanucleotide repeat in different motor neuron diseases. Neurobiol Aging 35:1214.e1211–1214.e1216. doi: 10.1016/j.neurobiolaging.2013.11.034 CrossRefGoogle Scholar
  34. 34.
    Jefferies HBJ, Cooke FT, Jat P, Boucheron C, Koizumi T, Hayakawa M et al (2008) A selective PIKfyve inhibitor blocks PtdIns(3,5)P(2) production and disrupts endomembrane transport and retroviral budding. EMBO Rep 9:164–170. doi: 10.1038/sj.embor.7401155 CrossRefPubMedPubMedCentralGoogle Scholar
  35. 35.
    Jones DA, Abbassi O, McIntire LV, McEver RP, Smith CW (1993) P-selectin mediates neutrophil rolling on histamine-stimulated endothelial cells. Biophys J 65:1560–1569. doi: 10.1016/s0006-3495(93)81195-0 CrossRefPubMedPubMedCentralGoogle Scholar
  36. 36.
    Kawamata T, Akiyama H, Yamada T, McGeer PL (1992) Immunologic reactions in amyotrophic lateral sclerosis brain and spinal cord tissue. Am J Pathol 140:691–707PubMedPubMedCentralGoogle Scholar
  37. 37.
    Kim HJ, Kim NC, Wang YD, Scarborough EA, Moore J, Diaz Z et al (2013) Prion-like domain mutations in hnRNPs cause multisystem proteinopathy and ALS. Nature 495:467–473. doi: 10.1038/nature11922 CrossRefPubMedPubMedCentralGoogle Scholar
  38. 38.
    Klussmann S, Martin-Villalba A (2005) Molecular targets in spinal cord injury. J Mol Med 83:657–671. doi: 10.1007/s00109-005-0663-3 CrossRefPubMedGoogle Scholar
  39. 39.
    Korn EL, Troendle JF, McShane LM, Simon R (2004) Controlling the number of false discoveries: application to high-dimensional genomic data. J Stat Plan Inference 124:379–398. doi: 10.1016/S0378-3758(03)00211-8 CrossRefGoogle Scholar
  40. 40.
    Kreutzberg GW (1996) Microglia: a sensor for pathological events in the CNS. Trends Neurosci 19:312–318. doi: 10.1016/0166-2236(96)10049-7 CrossRefPubMedGoogle Scholar
  41. 41.
    Kuhle J, Lindberg RLP, Regeniter A, Mehling M, Steck AJ, Kappos L et al (2009) Increased levels of inflammatory chemokines in amyotrophic lateral sclerosis. Eur J Neurol 16:771–774. doi: 10.1111/j.1468-1331.2009.02560.x CrossRefPubMedGoogle Scholar
  42. 42.
    Lehnert S, Costa J, de Carvalho M, Kirby J, Kuzma-Kozakiewicz M, Morelli C et al (2014) Multicentre quality control evaluation of different biomarker candidates for amyotrophic lateral sclerosis. Amyotroph Lateral Scler Frontotemporal Degener 15:344–350. doi: 10.3109/21678421.2014.884592 CrossRefPubMedGoogle Scholar
  43. 43.
    Liao B, Zhao W, Beers DR, Henkel JS, Appel SH (2012) Transformation from a neuroprotective to a neurotoxic microglial phenotype in a mouse model of ALS. Exp Neurol 237:147–152. doi: 10.1016/j.expneurol.2012.06.011 CrossRefPubMedPubMedCentralGoogle Scholar
  44. 44.
    44. Lincecum JM, Vieira FG, Wang MZ, Thompson K, De Zutter GS, Kidd J et al. (2010) From transcriptome analysis to therapeutic anti-CD40L treatment in the SOD1 model of amyotrophic lateral sclerosis. Nat Genet 42: 392–399.
  45. 45.
    Mantovani S, Garbelli S, Pasini A, Alimonti D, Perotti C, Melazzini M et al (2009) Immune system alterations in sporadic amyotrophic lateral sclerosis patients suggest an ongoing neuroinflammatory process. J Neuroimmunol 210:73–79. doi: 10.1016/j.jneuroim.2009.02.012 CrossRefPubMedGoogle Scholar
  46. 46.
    Mildner A, Schmidt H, Nitsche M, Merkler D, Hanisch UK, Mack M et al. (2007) Microglia in the adult brain arise from Ly-6ChiCCR2 + monocytes only under defined host conditions. Nat Neurosci 10:1544–1553.
  47. 47.
    Mitchell AJ, Roediger B, Weninger W (2014) Monocyte homeostasis and the plasticity of inflammatory monocytes. Cell Immunol 291:22–31. doi: 10.1016/j.cellimm.2014.05.010 CrossRefPubMedGoogle Scholar
  48. 48.
    Murdock BJ, Bender DE, Segal BM, Feldman EL (2015) The dual roles of immunity in ALS: injury overrides protection. Neurobiol Disease 77:1–12. doi: 10.1016/j.nbd.2015.02.017 CrossRefGoogle Scholar
  49. 49.
    Nagelkerke SQ, Kuijpers TW (2014) Immunomodulation by IVIg and the role of Fc-gamma receptors: classic mechanisms of action after all? Front Immunol 5:674. doi: 10.3389/fimmu.2014.00674 PubMedGoogle Scholar
  50. 50.
    Nimmerjahn F, Ravetch JV (2008) Fc[gamma] receptors as regulators of immune responses. Nat Rev Immunol 8:34–47CrossRefPubMedGoogle Scholar
  51. 51.
    Nourshargh S, Alon R (2014) Leukocyte migration into inflamed tissues. Immunity 41:694–707. doi: 10.1016/j.immuni.2014.10.008 CrossRefPubMedGoogle Scholar
  52. 52.
    O’Neill ASG, van den Berg TK, Mullen GED (2013) Sialoadhesin: a macrophage-restricted marker of immunoregulation and inflammation. Immunology 138:198–207. doi: 10.1111/imm.12042 CrossRefPubMedPubMedCentralGoogle Scholar
  53. 53.
    Overdijk MB, Verploegen S, Ortiz Buijsse A, Vink T, Leusen JHW, Bleeker WK et al (2012) Crosstalk between human IgG isotypes and murine effector cells. J Immunol 189:3430–3438. doi: 10.4049/jimmunol.1200356 CrossRefPubMedGoogle Scholar
  54. 54.
    Pfaffl MW (2001) A new mathematical model for relative quantification in real-time RT–PCR. Nucleic Acids Res 29:e45CrossRefPubMedPubMedCentralGoogle Scholar
  55. 55.
    Randolph GJ, Jakubzick C, Qu C (2008) Antigen presentation by monocytes and monocyte-derived cells. Curr Opin Immunol 20:52–60. doi: 10.1016/j.coi.2007.10.010 CrossRefPubMedGoogle Scholar
  56. 56.
    Rempel H, Calosing C, Sun B, Pulliam L (2008) Sialoadhesin expressed on IFN-induced monocytes binds HIV-1 and enhances infectivity. PLoS One 3:e1967. doi: 10.1371/journal.pone.0001967 CrossRefPubMedPubMedCentralGoogle Scholar
  57. 57.
    Renton AE, Majounie E, Waite A, Simón-Sánchez J, Rollinson S, Gibbs JR et al (2011) A hexanucleotide repeat expansion in C9ORF72 is the cause of chromosome 9p21-linked ALS-FTD. Neuron 72:257–268. doi: 10.1016/j.neuron.2011.09.010 CrossRefPubMedPubMedCentralGoogle Scholar
  58. 58.
    Robberecht W, Philips T (2013) The changing scene of amyotrophic lateral sclerosis. Nat Rev Neurosci 14: 248–264.
  59. 59.
    Ryberg H, An J, Darko S, Lustgarten JL, Jaffa M, Gopalakrishnan V et al (2010) Discovery and verification of amyotrophic lateral sclerosis biomarkers by proteomics. Muscle Nerve 42:104–111. doi: 10.1002/mus.21683 CrossRefPubMedPubMedCentralGoogle Scholar
  60. 60.
    Shi C, Pamer EG (2011) Monocyte recruitment during infection and inflammation. Nat Rev Immunol 11:762–774. doi: 10.1038/nri3070 CrossRefPubMedPubMedCentralGoogle Scholar
  61. 61.
    Steiniger B, Barth P, Herbst B, Hartnell A, Crocker PR (1997) The species-specific structure of microanatomical compartments in the human spleen: strongly sialoadhesin-positive macrophages occur in the perifollicular zone, but not in the marginal zone. Immunology 92:307–316CrossRefPubMedPubMedCentralGoogle Scholar
  62. 62.
    Tanaka M, Krutzik SR, Sieling PA, Lee D, Rea TH, Modlin RL (2009) Activation of FcγR1 on monocytes triggers differentiation into immature dendritic cells that induce autoreactive T cell responses. J Immunol (Baltimore, Md : 1950) 183:2349–2355. doi: 10.4049/jimmunol.0801683 CrossRefGoogle Scholar
  63. 63.
    Turner MR, Cagnin A, Turkheimer FE, Miller CCJ, Shaw CE, Brooks DJ et al (2004) Evidence of widespread cerebral microglial activation in amyotrophic lateral sclerosis: an [11C](R)-PK11195 positron emission tomography study. Neurobiol Disease 15:601–609. doi: 10.1016/j.nbd.2003.12.012 CrossRefGoogle Scholar
  64. 64.
    Weydt P, Hong SY, Kliot M, Möller T (2003) Assessing disease onset and progression in the SOD1 mouse model of ALS. NeuroReport 14:1051–1054. doi: 10.1097/01.wnr.0000073685.00308.89 CrossRefPubMedGoogle Scholar
  65. 65.
    Wiesner D, Merdian I, Lewerenz J, Ludolph AC, Dupuis L, Witting A (2013) Fumaric Acid esters stimulate astrocytic VEGF expression through HIF-1α and Nrf2. PLoS One 8:e76670. doi: 10.1371/journal.pone.0076670 CrossRefPubMedPubMedCentralGoogle Scholar
  66. 66.
    Witting A, Möller T (2011) Microglia cell culture: a primer for the novice. In Vitro Neurotoxicology. Humana Press, New York, pp 49–66CrossRefGoogle Scholar
  67. 67.
    Yamasaki R, Lu H, Butovsky O, Ohno N, Rietsch AM, Cialic R et al (2014) Differential roles of microglia and monocytes in the inflamed central nervous system. J Exp Med 211:1533–1549. doi: 10.1084/jem.20132477 CrossRefPubMedPubMedCentralGoogle Scholar
  68. 68.
    York MR, Nagai T, Mangini AJ, Lemaire R, van Seventer JM, Lafyatis R (2007) A macrophage marker, siglec-1, is increased on circulating monocytes in patients with systemic sclerosis and induced by type i interferons and toll-like receptor agonists. Arthritis Rheum 56:1010–1020. doi: 10.1002/art.22382 CrossRefPubMedGoogle Scholar
  69. 69.
    Ziegler-Heitbrock L (2014) Monocyte subsets in man and other species. Cell Immunol 289:135–139. doi: 10.1016/j.cellimm.2014.03.019 CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2016

Authors and Affiliations

  • Lisa Zondler
    • 1
  • Kathrin Müller
    • 1
  • Samira Khalaji
    • 2
  • Corinna Bliederhäuser
    • 1
  • Wolfgang P. Ruf
    • 1
  • Veselin Grozdanov
    • 1
  • Meinolf Thiemann
    • 4
  • Katrin Fundel-Clemes
    • 3
  • Axel Freischmidt
    • 1
  • Karlheinz Holzmann
    • 5
  • Benjamin Strobel
    • 3
  • Patrick Weydt
    • 1
  • Anke Witting
    • 1
  • Dietmar R. Thal
    • 1
  • Anika M. Helferich
    • 1
  • Bastian Hengerer
    • 3
  • Kay-Eberhard Gottschalk
    • 2
  • Oliver Hill
    • 4
  • Michael Kluge
    • 4
  • Albert C. Ludolph
    • 1
  • Karin M. Danzer
    • 1
  • Jochen H. Weishaupt
    • 1
  1. 1.Department of NeurologyUlm UniversityUlmGermany
  2. 2.Department of Experimental PhysicsUlm UniversityUlmGermany
  3. 3.Boehringer Ingelheim Pharma GmbH & Co. KGBiberachGermany
  4. 4.Apogenix GmbHHeidelbergGermany
  5. 5.Core Facility GenomicsUlm UniversityUlmGermany

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