Neuroscience Bulletin

, Volume 29, Issue 2, pp 189–198 | Cite as

Polarization of macrophages and microglia in inflammatory demyelination



Multiple sclerosis (MS) is an autoimmune demyelinating disease of the central nervous system, and microglia and macrophages play important roles in its pathogenesis. The activation of microglia and macrophages accompanies disease development, whereas depletion of these cells significantly decreases disease severity. Microglia and macrophages usually have diverse and plastic phenotypes. Both pro-inflammatory and antiinflammatory microglia and macrophages exist in MS and its animal model, experimental autoimmune encephalomyelitis. The polarization of microglia and macrophages may underlie the differing functional properties that have been reported. in this review, we discuss the responses and polarization of microglia and macrophages in MS, and their effects on its pathogenesis and repair. Harnessing their beneficial effects by modulating their polarization states holds great promise for the treatment of inflammatory demyelinating diseases.


macrophage microglia polarization demyelination remyelination 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. [1]
    Trapp BD, Bo L, Mork S, Chang A. Pathogenesis of tissue injury in MS lesions. J Neuroimmunol 1999, 98: 49–56.PubMedCrossRefGoogle Scholar
  2. [2]
    Dhib-Jalbut S. Pathogenesis of myelin/oligodendrocyte damage in multiple sclerosis. Neurology 2007, 68: S13–21; discussion S43–54.PubMedCrossRefGoogle Scholar
  3. [3]
    Guo MF, Ji N, Ma CG. Immunologic pathogenesis of multiple sclerosis. Neurosci Bull 2008, 24: 381–386.PubMedCrossRefGoogle Scholar
  4. [4]
    Barnett MH, Prineas JW. Relapsing and remitting multiple sclerosis: pathology of the newly forming lesion. Ann Neurol 2004, 55: 458–468.PubMedCrossRefGoogle Scholar
  5. [5]
    Henderson AP, Barnett MH, Parratt JD, Prineas JW. Multiple sclerosis: distribution of inflammatory cells in newly forming lesions. Ann Neurol 2009, 66: 739–753.PubMedCrossRefGoogle Scholar
  6. [6]
    Huitinga I, van Rooijen N, de Groot CJ, Uitdehaag BM, Dijkstra CD. Suppression of experimental allergic encephalomyelitis in Lewis rats after elimination of macrophages. J Exp Med 1990, 172: 1025–1033.PubMedCrossRefGoogle Scholar
  7. [7]
    Heppner FL, Greter M, Marino D, Falsig J, Raivich G, Hovelmeyer N, et al. Experimental autoimmune encephalomyelitis repressed by microglial paralysis. Nat Med 2005, 11: 146–152.PubMedCrossRefGoogle Scholar
  8. [8]
    David S, Kroner A. Repertoire of microglial and macrophage responses after spinal cord injury. Nat Rev Neurosci 2011, 12: 388–399.PubMedCrossRefGoogle Scholar
  9. [9]
    Shechter R, Schwartz M. Harnessing monocyte-derived macrophages to control central nervous system pathologies: no longer ‘if’ but ‘how’. J Pathol 2013, 229: 332–346.PubMedCrossRefGoogle Scholar
  10. [10]
    Butovsky O, Landa G, Kunis G, Ziv Y, Avidan H, Greenberg N, et al. Induction and blockage of oligodendrogenesis by differently activated microglia in an animal model of multiple sclerosis. J Clin Invest 2006, 116: 905–915.PubMedCrossRefGoogle Scholar
  11. [11]
    Mikita J, Dubourdieu-Cassagno N, Deloire MS, Vekris A, Biran M, Raffard G, et al. Altered M1/M2 activation patterns of monocytes in severe relapsing experimental rat model of multiple sclerosis. Amelioration of clinical status by M2 activated monocyte administration. Mult Scler 2011, 17: 2–15.PubMedCrossRefGoogle Scholar
  12. [12]
    Ponomarev ED, Veremeyko T, Barteneva N, Krichevsky AM, Weiner HL. MicroRNA-124 promotes microglia quiescence and suppresses EAE by deactivating macrophages via the C/EBP-alpha-PU.1 pathway. Nat Med 2011, 17: 64–70.PubMedCrossRefGoogle Scholar
  13. [13]
    Weber MS, Prod’homme T, Youssef S, Dunn SE, Rundle CD, Lee L, et al. Type ii monocytes modulate T cell-mediated central nervous system autoimmune disease. Nat Med 2007, 13: 935–943.PubMedCrossRefGoogle Scholar
  14. [14]
    Martinez FO, Helming L, Gordon S. Alternative activation of macrophages: an immunologic functional perspective. Annu Rev immunol 2009, 27: 451–483.PubMedCrossRefGoogle Scholar
  15. [15]
    Lawrence T, Natoli G. Transcriptional regulation of macrophage polarization: enabling diversity with identity. Nat Rev immunol 2011, 11: 750–761.PubMedCrossRefGoogle Scholar
  16. [16]
    Flavell RA, Sanjabi S, Wrzesinski SH, Licona-Limon P. The polarization of immune cells in the tumour environment by TGFbeta. Nat Rev Immunol 2010, 10: 554–567.PubMedCrossRefGoogle Scholar
  17. [17]
    Jang E, Lee S, Kim JH, Seo JW, Lee WH, Mori K, et al. Secreted protein lipocalin-2 promotes microglial M1 polarization. FASEB J 2013, 27: 1176–1190.PubMedCrossRefGoogle Scholar
  18. [18]
    Hu X, Li P, Guo Y, Wang H, Leak RK, Chen S, et al. Microglia/macrophage polarization dynamics reveal novel mechanism of injury expansion after focal cerebral ischemia. Stroke 2012, 43: 3063–3070.PubMedCrossRefGoogle Scholar
  19. [19]
    Mandrekar-Colucci S, Karlo JC, Landreth GE. Mechanisms underlying the rapid peroxisome proliferator-activated receptor-gamma-mediated amyloid clearance and reversal of cognitive deficits in a murine model of Alzheimer’s disease. J Neurosci 2012, 32: 10117–10128.PubMedCrossRefGoogle Scholar
  20. [20]
    Ponomarev ED, Veremeyko T, Weiner HL. MicroRNAs are universal regulators of differentiation, activation, and polarization of microglia and macrophages in normal and diseased CNS. Glia 2013, 61: 91–103.PubMedCrossRefGoogle Scholar
  21. [21]
    Durafourt BA, Moore CS, Zammit DA, Johnson TA, Zaguia F, Guiot MC, et al. Comparison of polarization properties of human adult microglia and blood-derived macrophages. Glia 2012, 60: 717–727.PubMedCrossRefGoogle Scholar
  22. [22]
    Ransohoff RM, Cardona AE. The myeloid cells of the central nervous system parenchyma. Nature 2010, 468: 253–262.PubMedCrossRefGoogle Scholar
  23. [23]
    Polfliet MM, van de Veerdonk F, Dopp EA, van Kesteren-Hendrikx EM, van Rooijen N, Dijkstra CD, et al. The role of perivascular and meningeal macrophages in experimental allergic encephalomyelitis. J Neuroimmunol 2002, 122: 1–8.PubMedCrossRefGoogle Scholar
  24. [24]
    Geissmann F, Jung S, Littman DR. Blood monocytes consist of two principal subsets with distinct migratory properties. immunity 2003, 19: 71–82.PubMedCrossRefGoogle Scholar
  25. [25]
    Sunderkotter C, Nikolic T, Dillon MJ, Van Rooijen N, Stehling M, Drevets DA, et al. Subpopulations of mouse blood monocytes differ in maturation stage and inflammatory response. J immunol 2004, 172: 4410–4417.PubMedGoogle Scholar
  26. [26]
    Fogg DK, Sibon C, Miled C, Jung S, Aucouturier P, Littman DR, et al. A clonogenic bone marrow progenitor specific for macrophages and dendritic cells. Science 2006, 311: 83–87.PubMedCrossRefGoogle Scholar
  27. [27]
    Mildner A, Mack M, Schmidt H, Bruck W, Djukic M, Zabel MD, et al. CCR2+Ly-6Chi monocytes are crucial for the effector phase of autoimmunity in the central nervous system. Brain 2009, 132: 2487–2500.PubMedCrossRefGoogle Scholar
  28. [28]
    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: 3190–3197.PubMedCrossRefGoogle Scholar
  29. [29]
    Saederup N, Cardona AE, Croft K, Mizutani M, Cotleur AC, Tsou CL, et al. Selective chemokine receptor usage by central nervous system myeloid cells in CCR2-red fluorescent protein knock-in mice. PLoS One 2010, 5: e13693.PubMedCrossRefGoogle Scholar
  30. [30]
    Ahn M, Yang W, Kim H, Jin JK, Moon C, Shin T. Immunohistochemical study of arginase-1 in the spinal cords of Lewis rats with experimental autoimmune encephalomyelitis. Brain Res 2012, 1453: 77–86.PubMedCrossRefGoogle Scholar
  31. [31]
    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: 641–651.PubMedCrossRefGoogle Scholar
  32. [32]
    Gao Z, Tsirka SE. Animal models of MS reveal multiple roles of microglia in disease pathogenesis. Neurol Res int 2011, 2011: 383087.PubMedGoogle Scholar
  33. [33]
    Ponomarev ED, Maresz K, Tan Y, Dittel BN. CNS-derived interleukin-4 is essential for the regulation of autoimmune inflammation and induces a state of alternative activation in microglial cells. J Neurosci 2007, 27: 10714–10721.PubMedCrossRefGoogle Scholar
  34. [34]
    Radtke C, Spies M, Sasaki M, Vogt PM, Kocsis JD. Demyelinating diseases and potential repair strategies. Int J Dev Neurosci 2007, 25: 149–153.PubMedCrossRefGoogle Scholar
  35. [35]
    Lucchinetti C, Bruck W, Noseworthy J. Multiple sclerosis: recent developments in neuropathology, pathogenesis, magnetic resonance imaging studies and treatment. Curr opin Neurol 2001, 14: 259–269.PubMedCrossRefGoogle Scholar
  36. [36]
    Patrizio M, Levi G. Glutamate production by cultured microglia: differences between rat and mouse, enhancement by lipopolysaccharide and lack effect of HIV coat protein gp120 and depolarizing agents. Neurosci Lett 1994, 178: 184–189.PubMedCrossRefGoogle Scholar
  37. [37]
    Zajicek JP, Wing M, Scolding NJ, Compston DA. Interactions between oligodendrocytes and microglia. A major role for complement and tumour necrosis factor in oligodendrocyte adherence and killing. Brain 1992, 115 (Pt 6): 1611–1631.PubMedGoogle Scholar
  38. [38]
    Merrill JE, Ignarro LJ, Sherman MP, Melinek J, Lane TE. Microglial cell cytotoxicity of oligodendrocytes is mediated through nitric oxide. J Immunol 1993, 151: 2132–2141.PubMedGoogle Scholar
  39. [39]
    Chakrabarty P, Ceballos-Diaz C, Beccard A, Janus C, Dickson D, Golde TE, et al. IFN-gamma promotes complement expression and attenuates amyloid plaque deposition in amyloid beta precursor protein transgenic mice. J Immunol 2010, 184: 5333–5343.PubMedCrossRefGoogle Scholar
  40. [40]
    Block ML, Zecca L, Hong JS. Microglia-mediated neurotoxicity: uncovering the molecular mechanisms. Nat Rev Neurosci 2007, 8: 57–69.PubMedCrossRefGoogle Scholar
  41. [41]
    Kuhlmann T, Miron V, Cui Q, Wegner C, Antel J, Bruck W. Differentiation block of oligodendroglial progenitor cells as a cause for remyelination failure in chronic multiple sclerosis. Brain 2008, 131: 1749–1758.PubMedCrossRefGoogle Scholar
  42. [42]
    Wolswijk G. Chronic stage multiple sclerosis lesions contain a relatively quiescent population of oligodendrocyte precursor cells. J Neurosci 1998, 18: 601–609.PubMedGoogle Scholar
  43. [43]
    Hanafy KA, Sloane JA. Regulation of remyelination in multiple sclerosis. FEBS Lett 2011, 585: 3821–3828.PubMedCrossRefGoogle Scholar
  44. [44]
    Chang A, Tourtellotte WW, Rudick R, Trapp BD. Premyelinating oligodendrocytes in chronic lesions of multiple sclerosis. N Engl J Med 2002, 346: 165–173.PubMedCrossRefGoogle Scholar
  45. [45]
    Rasmussen S, Imitola J, Ayuso-Sacido A, Wang Y, Starossom SC, Kivisakk P, et al. Reversible neural stem cell niche dysfunction in a model of multiple sclerosis. Ann Neurol 2011, 69: 878–891.PubMedCrossRefGoogle Scholar
  46. [46]
    Pluchino S, Muzio L, Imitola J, Deleidi M, Alfaro-Cervello C, Salani G, et al. Persistent inflammation alters the function of the endogenous brain stem cell compartment. Brain 2008, 131: 2564–2578.PubMedCrossRefGoogle Scholar
  47. [47]
    Tepavcevic V, Lazarini F, Alfaro-Cervello C, Kerninon C, Yoshikawa K, Garcia-Verdugo JM, et al. Inflammationinduced subventricular zone dysfunction leads to olfactory deficits in a targeted mouse model of multiple sclerosis. J Clin invest 2011, 121: 4722–4734.PubMedCrossRefGoogle Scholar
  48. [48]
    Rasmussen S, Wang Y, Kivisakk P, Bronson RT, Meyer M, Imitola J, et al. Persistent activation of microglia is associated with neuronal dysfunction of callosal projecting pathways and multiple sclerosis-like lesions in relapsing—remitting experimental autoimmune encephalomyelitis. Brain 2007, 130: 2816–2829.PubMedCrossRefGoogle Scholar
  49. [49]
    Butovsky O, Ziv Y, Schwartz A, Landa G, Talpalar AE, Pluchino S, et al. Microglia activated by IL-4 or IFN-gamma differentially induce neurogenesis and oligodendrogenesis from adult stem/progenitor cells. Mol Cell Neurosci 2006, 31: 149–160.PubMedCrossRefGoogle Scholar
  50. [50]
    Paintlia AS, Paintlia MK, Singh I, Singh AK. IL-4-induced peroxisome proliferator-activated receptor gamma activation inhibits NF-kappaB trans activation in central nervous system (CNS) glial cells and protects oligodendrocyte progenitors under neuroinflammatory disease conditions: implication for CNS-demyelinating diseases. J Immunol 2006, 176: 4385–4398.PubMedGoogle Scholar
  51. [51]
    Kigerl KA, Gensel JC, Ankeny DP, Alexander JK, Donnelly DJ, Popovich PG. Identification of two distinct macrophage subsets with divergent effects causing either neurotoxicity or regeneration in the injured mouse spinal cord. J Neurosci 2009, 29: 13435–13444.PubMedCrossRefGoogle Scholar
  52. [52]
    Centonze D, Muzio L, Rossi S, Cavasinni F, De Chiara V, Bergami A, et al. Inflammation triggers synaptic alteration and degeneration in experimental autoimmune encephalomyelitis. J Neurosci 2009, 29: 3442–3452.PubMedCrossRefGoogle Scholar
  53. [53]
    Pitt D, Werner P, Raine CS. Glutamate excitotoxicity in a model of multiple sclerosis. Nat Med 2000, 6: 67–70.PubMedCrossRefGoogle Scholar
  54. [54]
    Haider L, Fischer MT, Frischer JM, Bauer J, Hoftberger R, Botond G, et al. Oxidative damage in multiple sclerosis lesions. Brain 2011, 134: 1914–1924.PubMedCrossRefGoogle Scholar
  55. [55]
    Fischer MT, Sharma R, Lim JL, Haider L, Frischer JM, Drexhage J, et al. NADPH oxidase expression in active multiple sclerosis lesions in relation to oxidative tissue damage and mitochondrial injury. Brain 2012, 135: 886–899.PubMedCrossRefGoogle Scholar
  56. [56]
    Doherty GH. Nitric oxide in neurodegeneration: potential benefits of non-steroidal anti-inflammatories. Neurosci Bull 2011, 27: 366–382.PubMedCrossRefGoogle Scholar
  57. [57]
    Kapoor R, Davies M, Blaker PA, Hall SM, Smith KJ. Blockers of sodium and calcium entry protect axons from nitric oxidemediated degeneration. Ann Neurol 2003, 53: 174–180.PubMedCrossRefGoogle Scholar
  58. [58]
    Bechtold DA, Kapoor R, Smith KJ. Axonal protection using flecainide in experimental autoimmune encephalomyelitis. Ann Neurol 2004, 55: 607–616.PubMedCrossRefGoogle Scholar
  59. [59]
    Black JA, Liu S, Waxman SG. Sodium channel activity modulates multiple functions in microglia. Glia 2009, 57: 1072–1081.PubMedCrossRefGoogle Scholar
  60. [60]
    Black JA, Waxman SG. Sodium channels and microglial function. Exp Neurol 2012, 234: 302–315.PubMedCrossRefGoogle Scholar
  61. [61]
    Craner MJ, Damarjian TG, Liu S, Hains BC, Lo AC, Black JA, et al. Sodium channels contribute to microglia/macrophage activation and function in EAE and MS. Glia 2005, 49: 220–229.PubMedCrossRefGoogle Scholar
  62. [62]
    Shijie J, Takeuchi H, Yawata I, Harada Y, Sonobe Y, Doi Y, et al. Blockade of glutamate release from microglia attenuates experimental autoimmune encephalomyelitis in mice. Tohoku J Exp Med 2009, 217: 87–92.PubMedCrossRefGoogle Scholar
  63. [63]
    Starossom SC, Mascanfroni ID, Imitola J, Cao L, Raddassi K, Hernandez SF, et al. Galectin-1 deactivates classically activated microglia and protects from inflammation-induced neurodegeneration. immunity 2012, 37: 249–263.PubMedCrossRefGoogle Scholar
  64. [64]
    Prineas JW, Barnard RO, Kwon EE, Sharer LR, Cho ES. Multiple sclerosis: remyelination of nascent lesions. Ann Neurol 1993, 33: 137–151.PubMedCrossRefGoogle Scholar
  65. [65]
    Prineas JW, Kwon EE, Cho ES, Sharer LR. Continual breakdown and regeneration of myelin in progressive multiple sclerosis plaques. Ann N Y Acad Sci 1984, 436: 11–32.PubMedCrossRefGoogle Scholar
  66. [66]
    Gitik M, Liraz-Zaltsman S, Oldenborg PA, Reichert F, Rotshenker S. Myelin down-regulates myelin phagocytosis by microglia and macrophages through interactions between CD47 on myelin and SiRPalpha (signal regulatory protein-alpha) on phagocytes. J Neuroinflammation 2011, 8: 24.PubMedCrossRefGoogle Scholar
  67. [67]
    Koning N, Bo L, Hoek RM, Huitinga I. Downregulation of macrophage inhibitory molecules in multiple sclerosis lesions. Ann Neurol 2007, 62: 504–514.PubMedCrossRefGoogle Scholar
  68. [68]
    Han MH, Lundgren DH, Jaiswal S, Chao M, Graham KL, Garris CS, et al. Janus-like opposing roles of CD47 in autoimmune brain inflammation in humans and mice. J Exp Med 2012, 209: 1325–1334.PubMedCrossRefGoogle Scholar
  69. [69]
    Williams K, Ulvestad E, Waage A, Antel JP, McLaurin J. Activation of adult human derived microglia by myelin phagocytosis in vitro. J Neurosci Res 1994, 38: 433–443.PubMedCrossRefGoogle Scholar
  70. [70]
    van der Laan LJ, Ruuls SR, Weber KS, Lodder IJ, Dopp EA, Dijkstra CD. Macrophage phagocytosis of myelin in vitro determined by flow cytometry: phagocytosis is mediated by CR3 and induces production of tumor necrosis factor-alpha and nitric oxide. J Neuroimmunol 1996, 70: 145–152.PubMedCrossRefGoogle Scholar
  71. [71]
    Sun X, Wang X, Chen T, Li T, Cao K, Lu A, et al. Myelin activates FAK/Akt/NF-kappaB pathways and provokes CR3-dependent inflammatory response in murine system. PLoS one 2010, 5: e9380.PubMedCrossRefGoogle Scholar
  72. [72]
    Boven LA, Van Meurs M, Van Zwam M, Wierenga-Wolf A, Hintzen RQ, Boot RG, et al. Myelin-laden macrophages are anti-inflammatory, consistent with foam cells in multiple sclerosis. Brain 2006, 129: 517–526.PubMedCrossRefGoogle Scholar
  73. [73]
    Liu Y, Hao W, Letiembre M, Walter S, Kulanga M, Neumann H, et al. Suppression of microglial inflammatory activity by myelin phagocytosis: role of p47-PHoX-mediated generation of reactive oxygen species. J Neurosci 2006, 26: 12904–12913.PubMedCrossRefGoogle Scholar
  74. [74]
    van Rossum D, Hilbert S, Strassenburg S, Hanisch UK, Bruck W. Myelin-phagocytosing macrophages in isolated sciatic and optic nerves reveal a unique reactive phenotype. Glia 2008, 56: 271–283.PubMedCrossRefGoogle Scholar
  75. [75]
    Smith ME, van der Maesen K, Somera FP. Macrophage and microglial responses to cytokines in vitro: phagocytic activity, proteolytic enzyme release, and free radical production. J Neurosci Res 1998, 54: 68–78.PubMedCrossRefGoogle Scholar
  76. [76]
    Gratchev A, Kzhyshkowska J, Utikal J, Goerdt S. Interleukin-4 and dexamethasone counterregulate extracellular matrix remodelling and phagocytosis in type-2 macrophages. Scand J Immunol 2005, 61: 10–17.PubMedCrossRefGoogle Scholar
  77. [77]
    Bauer J, Sminia T, Wouterlood FG, Dijkstra CD. Phagocytic activity of macrophages and microglial cells during the course of acute and chronic relapsing experimental autoimmune encephalomyelitis. J Neurosci Res 1994, 38: 365–375.PubMedCrossRefGoogle Scholar
  78. [78]
    Wu M, Tsirka SE. Endothelial NOS-deficient mice reveal dual roles for nitric oxide during experimental autoimmune encephalomyelitis. Glia 2009, 57: 1204–1215.PubMedCrossRefGoogle Scholar
  79. [79]
    Gandhi R, Laroni A, Weiner HL. Role of the innate immune system in the pathogenesis of multiple sclerosis. J Neuroimmunol 2010, 221: 7–14.PubMedCrossRefGoogle Scholar
  80. [80]
    Chastain EM, Duncan DS, Rodgers JM, Miller SD. The role of antigen presenting cells in multiple sclerosis. Biochim Biophys Acta 2011, 1812: 265–274.PubMedCrossRefGoogle Scholar
  81. [81]
    Becher B, Bechmann I, Greter M. Antigen presentation in autoimmunity and CNS inflammation: how T lymphocytes recognize the brain. J Mol Med (Berl) 2006, 84: 532–543.CrossRefGoogle Scholar
  82. [82]
    Fletcher JM, Lalor SJ, Sweeney CM, Tubridy N, Mills KH. T cells in multiple sclerosis and experimental autoimmune encephalomyelitis. Clin Exp Immunol 2010, 162: 1–11.PubMedCrossRefGoogle Scholar
  83. [83]
    Das J, Ren G, Zhang L, Roberts AI, Zhao X, Bothwell AL, et al. Transforming growth factor beta is dispensable for the molecular orchestration of Th17 cell differentiation. J Exp Med 2009, 206: 2407–2416.PubMedCrossRefGoogle Scholar
  84. [84]
    Das Sarma J, Ciric B, Marek R, Sadhukhan S, Caruso ML, Shafagh J, et al. Functional interleukin-17 receptor A is expressed in central nervous system glia and upregulated in experimental autoimmune encephalomyelitis. J Neuroinflammation 2009, 6: 14.PubMedCrossRefGoogle Scholar
  85. [85]
    Olson JK, Miller SD. Microglia initiate central nervous system innate and adaptive immune responses through multiple TLRs. J Immunol 2004, 173: 3916–3924.PubMedGoogle Scholar
  86. [86]
    Eugenin EA, Osiecki K, Lopez L, Goldstein H, Calderon TM, Berman JW. CCL2/monocyte chemoattractant protein-1 mediates enhanced transmigration of human immunodeficiency virus (HIV)-infected leukocytes across the blood-brain barrier: a potential mechanism of HiV-CNS invasion and NeuroAiDS. J Neurosci 2006, 26: 1098–1106.PubMedCrossRefGoogle Scholar
  87. [87]
    Muller M, Carter SL, Hofer MJ, Manders P, Getts DR, Getts MT, et al. CXCR3 signaling reduces the severity of experimental autoimmune encephalomyelitis by controlling the parenchymal distribution of effector and regulatory T cells in the central nervous system. J Immunol 2007, 179: 2774–2786.PubMedGoogle Scholar
  88. [88]
    Dogan RN, Long N, Forde E, Dennis K, Kohm AP, Miller SD, et al. CCL22 regulates experimental autoimmune encephalomyelitis by controlling inflammatory macrophage accumulation and effector function. J Leukoc Biol 2011, 89: 93–104.PubMedCrossRefGoogle Scholar

Copyright information

© Shanghai Institutes for Biological Sciences, CAS and Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  1. 1.Institute of Neuroscience and Key Laboratory of Molecular Neurobiology of the Ministry of Education, Neuroscience Research Center of Changzheng HospitalSecond Military Medical UniversityShanghaiChina

Personalised recommendations