How type I interferons shape myeloid cell function in CNS autoimmunity

Journal of Leukocyte Biology

Volumn 92, Issue 3, 2012, Pages 479-488

  Brendecke, Stefanie M ^a   Prinz, Marco ^a  

^a UNIVERSITY OF FREIBURG   (Germany)

Author keywords

EAE; Inflammasome; Microglia; MS; TRAIL

Indexed keywords

B7 ANTIGEN; BETA INTERFERON; CD40 ANTIGEN; CYTOTOXIC T LYMPHOCYTE ANTIGEN 4; GAMMA INTERFERON; INTERFERON; INTERLEUKIN 10; INTERLEUKIN 12; INTERLEUKIN 18; INTERLEUKIN 1BETA; INTERLEUKIN 23; INTERLEUKIN 27; INTERLEUKIN 4; INTERLEUKIN 5; STAT1 PROTEIN; STAT3 PROTEIN; TUMOR NECROSIS FACTOR RELATED APOPTOSIS INDUCING LIGAND;

ADAPTIVE IMMUNITY; ANTIGEN PRESENTATION; ANTIGEN PRESENTING CELL; APOPTOSIS; AUTOIMMUNITY; BONE MARROW CELL; CANDIDA ALBICANS; CD4+ CD25+ T LYMPHOCYTE; CD4+ T LYMPHOCYTE; CELL ACTIVATION; CELL EXPANSION; CELL FUNCTION; CELL MATURATION; CELL SURVIVAL; CENTRAL NERVOUS SYSTEM; CYTOKINE PRODUCTION; CYTOKINE RELEASE; DENDRITIC CELL; DOWN REGULATION; GENE EXPRESSION; HUMAN; INNATE IMMUNITY; LISTERIA MONOCYTOGENES; LYMPHOCYTE DIFFERENTIATION; MACROPHAGE; MICROGLIA; MULTIPLE SCLEROSIS; NATURAL KILLER CELL; NONHUMAN; PATHOGENESIS; PHAGOCYTOSIS; PRIORITY JOURNAL; REVIEW; SIGNAL TRANSDUCTION; T LYMPHOCYTE ACTIVATION; TH17 CELL; UPREGULATION;

ANTIGEN PRESENTATION; AUTOIMMUNITY; DEMYELINATING AUTOIMMUNE DISEASES, CNS; HUMANS; INTERFERON TYPE I; LYMPHOCYTE ACTIVATION; MYELOID CELLS;

EID: 84865501599     PISSN: 07415400     EISSN: None     Source Type: Journal    
DOI: 10.1189/jlb.0112043     Document Type: Review

References (89)

1. Gonzalez-Navajas, J. M., Lee, J., David, M., Raz, E. (2012) Immunomodulatory functions of type I interferons. Nat. Rev. Immunol.12, 125
2. Hervas-Stubbs, S., Perez-Gracia, J. L., Rouzaut, A., Sanmamed, M. F., Le Bon, A., Melero, I. (2011) Direct effects of type I interferons on cells of the immune system. Clin. Cancer Res. 17, 2619-2627.
3. Prinz, M., Schmidt, H., Mildner, A., Knobeloch, K. P., Hanisch, U. K., Raasch, J., Merkler, D., Detje, C., Gutcher, I., Mages, J., Lang, R., Martin, R., Gold, R., Becher, B., Bruck, W., Kalinke, U. (2008) Distinct and nonredundant in vivo functions of IFNAR on myeloid cells limit autoimmunity in the central nervous system. Immunity 28, 675-686.
4. Steinman, L., Merrill, J. T., McInnes, I. B., Peakman, M. (2012) Optimization of current and future therapy for autoimmune diseases. Nat. Med. 18, 59-65.
5. Weiner, H. L. (2004) Multiple sclerosis is an inflammatory T-cell-medi-ated autoimmune disease. Arch. Neurol. 61, 1613-1615.
6. PRISMS (Prevention of Relapses and Disability by Interferon β-1a Subcutaneously in Multiple Sclerosis) Study Group. (1998) Randomised double-blind placebo-controlled study of interferon β-^ in relapsing/ remitting multiple sclerosis. Lancet 352, 1498-1504.
7. Singh, A. K., Wilson, M. T., Hong, S., Olivares-Villagomez, D., Du, C., Stanic, A. K., Joyce, S., Sriram, S., Koezuka, Y., Van Kaer, L. (2001) Natural killer T cell activation protects mice against experimental autoimmune encephalomyelitis. J. Exp. Med. 194, 1801-1811.
8. Owens, T., Wekerle, H., Antel, J. (2001) Genetic models for CNS inflammation. Nat. Med. 7, 161-166.
9. Teige, I., Treschow, A., Teige, A., Mattsson, R., Navikas, V., Leanderson, T., Holmdahl, R., Issazadeh-Navikas, S. (2003) IFN-β gene deletion leads to augmented and chronic demyelinating experimental autoimmune encephalomyelitis. J. Immunol. 170, 4776-4784.
10. Uzawa, A., Mori, M., Hayakawa, S., Masuda, S., Kuwabara, S. (2010) Different responses to interferon β-^ treatment in patients with neuromyelitis optica and multiple sclerosis. Eur. J. Neurol. 17, 672-676.
11. Neilley, L. K., Goodin, D. S., Goodkin, D. E., Hauser, S. L. (1996) Side effect profile of interferon β-^ in MS: results of an open label trial. Neurology 46, 552-554.
12. Dhib-Jalbut, S., Marks, S. (2010) Interferon-β mechanisms of action in multiple sclerosis. Neurology 74 (Suppl. 1), S17-S24.
13. Guo, B., Chang, E. Y., Cheng, G. (2008) The type I IFN induction pathway constrains Th17-mediated autoimmune inflammation in mice. J. Clin. Invest. 118, 1680-1690.
14. Prinz, M., Kalinke, U. (2010) New lessons about old molecules: how type I interferons shape Th1/Th17-mediated autoimmunity in the CNS. Trends Mol. Med. 16, 379-386.
15. Banchereau, J., Steinman, R. M. (1998) Dendritic cells and the control of immunity. Nature 392, 245-252.
16. Hur, E. M., Youssef, S., Haws, M. E., Zhang, S. Y., Sobel, R. A., Stein-man, L. (2007) Osteopontin-induced relapse and progression of autoimmune brain disease through enhanced survival of activated T cells. Nat. Immunol. 8, 74-83.
17. Fujiwara, N., Kobayashi, K (2005) Macrophages in inflammation. Curr. Drug Targets Inflamm. Allergy 4, 281-286.
18. Chastain, E. M., Duncan, D. S., Rodgers, J. M., Miller, S. D. (2011) The role of antigen presenting cells in multiple sclerosis. Biochim. Biophys. Acta 1812, 265-274.
19. Gigli, G., Caielli, S., Cutuli, D., Falcone, M. (2007) Innate immunity modulates autoimmunity: type 1 interferon-β treatment in multiple sclerosis promotes growth and function of regulatory invariant natural killer T cells through dendritic cell maturation. Immunology 122, 409-417.
20. Schreiner, B., Mitsdoerffer, M., Kieseier, B. C., Chen, L., Hartung, H. P., Weller, M., Wiendl, H. (2004) Interferon-β enhances monocyte and dendritic cell expression of B7-H1 (PD-L1), a strong inhibitor of autologous T-cell activation: relevance for the immune modulatory effect in multiple sclerosis. J. Neuroimmunol. 155, 172-182.
21. Chen, M., Chen, G., Deng, S., Liu, X., Hutton, G.J., Hong, J. (2012) IFN-β induces the proliferation of CD4(+)CD25(+)Foxp3(+) regulatory T cells through upregulation of GITRL on dendritic cells in the treatment of multiple sclerosis. J. Neuroimmunol. 242, 39-46.
22. Serafini, B., Rosicarelli, B., Magliozzi, R., Stigliano, E., Capello, E., Man-cardi, G. L., Aloisi, F. (2006) Dendritic cells in multiple sclerosis lesions: maturation stage, myelin uptake, and interaction with proliferating T cells. J. Neuropathol. Exp. Neurol. 65, 124-141.
23. Zozulya, A. L., Clarkson, B. D., Ortler, S., Fabry, Z., Wiendl, H. (2010) The role of dendritic cells in CNS autoimmunity. J. Mol. Med. (Berl). 88, 535-544.
24. Huang, D. R., Wang, J., Kivisakk, P., Rollins, B. J., Ransohoff, R. M. (2001) Absence of monocyte chemoattractant protein 1 in mice leads to decreased local macrophage recruitment and antigen-specific T helper cell type 1 immune response in experimental autoimmune encephalomyelitis. J. Exp. Med. 193, 713-726.
25. Steinman, R. M. (2007) Dendritic cells: understanding immunogenicity. Eur. J. Immunol. 37 (Suppl. 1), S53-S60.
26. Le Bon, A., Tough, D. F. (2008) Type I interferon as a stimulus for cross-priming. Cytokine Growth Factor Rev. 19, 33-40.
27. Marckmann, S., Wiesemann, E., Hilse, R., Trebst, C., Stangel, M., Wind-hagen, A. (2004) Interferon-β up-regulates the expression of co-stimulatory molecules CD80, CD86 and CD40 on monocytes: significance for treatment of multiple sclerosis. Clin. Exp. Immunol. 138, 499-506.
28. Zang, Y. C., Skinner, S. M., Robinson, R. R., Li, S., Rivera, V. M., Hutton, G. J., Zhang, J. Z. (2004) Regulation of differentiation and functional properties of monocytes and monocyte-derived dendritic cells by interferon β in multiple sclerosis. Mult. Scler. 10, 499-506.
29. Jahng, A. W., Maricic, I., Pedersen, B., Burdin, N., Naidenko, O., Kro-nenberg, M., Koezuka, Y., Kumar, V. (2001) Activation of natural killer T cells potentiates or prevents experimental autoimmune encephalomyelitis. J. Exp. Med. 194, 1789-1799.
30. Hegde, S., Fox, L., Wang, X., Gumperz, J. E. (2010) Autoreactive natural killer T cells: promoting immune protection and immune tolerance through varied interactions with myeloid antigen-presenting cells. Immunology 130, 471-483.
31. Dong, H., Zhu, G., Tamada, K, Chen, L. (1999) B7-H1, a third member of the B7 family, co-stimulates T-cell proliferation and interleukin-10 secretion. Nat. Med. 5, 1365-1369.
32. Racke, M. K., Ratts, R. B., Arredondo, L., Perrin, P. J., Lovett-Racke, A. (2000) The role of costimulation in autoimmune demyelination. J. Neu-roimmunol. 107, 205-215.
33. Hirata, S., Senju, S., Matsuyoshi, H., Fukuma, D., Uemura, Y., Nishimura, Y. (2005) Prevention of experimental autoimmune encephalomyelitis by transfer of embryonic stem cell-derived dendritic cells expressing myelin oligodendrocyte glycoprotein peptide along with TRAIL or programmed death-1 ligand. J. Immunol. 174, 1888-1897.
34. Le Bon, A., Etchart, N., Rossmann, C., Ashton, M., Hou, S., Gewert, D., Borrow, P., Tough, D. F. (2003) Cross-priming of CD8+ T cells stimulated by virus-induced type I interferon. Nat. Immunol. 4, 1009-1015.
35. Ito, T., Amakawa, R., Inaba, M., Ikehara, S., Inaba, K, Fukuhara, S. (2001) Differential regulation of human blood dendritic cell subsets by IFNs. J. Immunol. 166, 2961-2969.
36. Gallucci, S., Lolkema, M., Matzinger, P. (1999) Natural adjuvants: endogenous activators of dendritic cells. Nat. Med. 5, 1249-1255.
37. Wang, X., Chen, M., Wandinger, K. P., Williams, G., Dhib-Jalbut, S. (2000) IFN^-1b inhibits IL-12 production in peripheral blood mononuclear cells in an IL-10-dependent mechanism: relevance to IFN^1b therapeutic effects in multiple sclerosis. J. Immunol. 165, 548-557.
38. Bettelli, E., Oukka, M., Kuchroo, V. K (2007) T(H)-17 cells in the circle of immunity and autoimmunity. Nat. Immunol. 8, 345-350.
39. Steinman, L. (2007) A brief history of T(H)17, the first major revision in the T(H)1/T(H)2 hypothesis of T cell-mediated tissue damage. Nat. Med. 13, 139-145.
40. Batten, M., Li, J., Yi, S., Kljavin, N. M., Danilenko, D. M., Lucas, S., Lee, J., de Sauvage, F. J., Ghilardi, N. (2006) Interleukin 27 limits autoimmune encephalomyelitis by suppressing the development of interleukin 17-producing T cells. Nat. Immunol. 7, 929-936.
41. Hofstetter, H. H., Ibrahim, S. M., Koczan, D., Kruse, N., Weishaupt, A., Toyka, K. V., Gold, R. (2005) Therapeutic efficacy of IL-17 neutralization in murine experimental autoimmune encephalomyelitis. Cell. Immunol. 237, 123-130.
42. McGeachy, M. J., Chen, Y., Tato, C. M., Laurence, A., Joyce-Shaikh, B., Blumenschein, W. M., McClanahan, T. K, O'Shea, J. J., Cua, D.J. (2009) The interleukin 23 receptor is essential for the terminal differentiation of interleukin 17-producing effector T helper cells in vivo. Nat. Immunol. 10, 314-324.
43. Fitzgerald, D. C., Zhang, G. X., El-Behi, M., Fonseca-Kelly, Z., Li, H., Yu, S., Saris, C. J., Gran, B., Ciric, B., Rostami, A. (2007) Suppression of autoimmune inflammation of the central nervous system by interleukin 10 secreted by interleukin 27-stimulated T cells. Nat. Immunol. 8, 13721379.
44. Axtell, R. C., de Jong, B. A., Boniface, K., van der Voort, L. F., Bhat, R., De Sarno, P., Naves, R., Han, M., Zhong, F., Castellanos, J. G., Mair, R., Christakos, A., Kolkowitz, I., Katz, L., Killestein, J., Polman, C. H., de Waal Malefyt, R., Steinman, L., Raman, C. (2010) T helper type 1 and 17 cells determine efficacy of interferon-β in multiple sclerosis and experimental encephalomyelitis. Nat. Med. 16, 406-412.
45. Shinohara, M. L., Kim, J. H., Garcia, V. A., Cantor, H. (2008) Engagement of the type I interferon receptor on dendritic cells inhibits T helper 17 cell development: role of intracellular osteopontin. Immunity 29, 68-78.
46. Ramgolam, V. S., Sha, Y., Jin, J., Zhang, X., Markovic-Plese, S. (2009) IFN-β inhibits human Th17 cell differentiation. J. Immunol. 183, 54185427.
47. Chabas, D., Baranzini, S. E., Mitchell, D., Bernard, C. C., Rittling, S. R., Denhardt, D. T., Sobel, R. A., Lock, C., Karpuj, M., Pedotti, R., Heller, R., Oksenberg, J. R., Steinman, L. (2001) The influence of the proin-flammatory cytokine, osteopontin, on autoimmune demyelinating disease. Science 294, 1731-1735.
48. Chen, M., Chen, G., Nie, H., Zhang, X., Niu, X., Zang, Y. C., Skinner, S. M., Zhang, J. Z., Killian, J. M., Hong, J. (2009) Regulatory effects of IFN-β on production of osteopontin and IL-17 by CD4+ T cells in MS. Eur. J. Immunol. 39, 2525-2536.
49. Shinohara, M. L., Kim, H. J., Kim, J. H., Garcia, V. A., Cantor, H. (2008) Alternative translation of osteopontin generates intracellular and secreted isoforms that mediate distinct biological activities in dendritic cells. Proc. Natl. Acad. Sci. USA 105, 7235-7239.
50. Jansson, M., Panoutsakopoulou, V., Baker, J., Klein, L., Cantor, H. (2002) Cutting edge: attenuated experimental autoimmune encephalomyelitis in η-1/osteopontin-deficient mice. J. Immunol. 168, 2096-2099.
51. Dann, A., Poeck, H., Croxford, A. L., Gaupp, S., Kierdorf, K, Knust, M., Pfeifer, D., Maihoefer, C., Endres, S., Kalinke, U., Meuth, S. G., Wiendl, H., Knobeloch, K. P., Akira, S., Waisman, A., Hartmann, G., Prinz, M. (2011) Cytosolic RIG-I-like helicases act as negative regulators of sterile inflammation in the CNS. Nat. Neurosci. 15, 98-106.
52. Gandhi, R., Laroni, A., Weiner, H. L. (2010) Role of the innate immune system in the pathogenesis of multiple sclerosis. J. Neuroimmunol. 221, 7-14.
53. Bogie, J. F., Stinissen, P., Hellings, N., Hendriks, J. J. (2011) Myelin-phagocytosing macrophages modulate autoreactive T cell proliferation. J. Neuroinflammation 8, 85.
54. LeBlanc, H. N., Ashkenazi, A. (2003) Apo2L/TRAIL and its death and decoy receptors. Cell Death Differ. 10, 66-75.
55. Lamhamedi-Cherradi, S. E., Zheng, S. J., Maguschak, K A., Peschon, J., Chen, Y. H. (2003) Defective thymocyte apoptosis and accelerated autoimmune diseases in TRAIL-/-mice. Nat. Immunol. 4, 255-260.
56. Ehrlich, S., Infante-Duarte, C., Seeger, B., Zipp, F. (2003) Regulation of soluble and surface-bound TRAIL in human T cells, B cells, and monocytes. Cytokine 24, 244-253.
57. Tecchio, C., Huber, V., Scapini, P., Calzetti, F., Margotto, D., Tode-schini, G., Pilla, L., Martinelli, G., Pizzolo, G., Rivoltini, L., Cassatella, M. A. (2004) IFNa-stimulated neutrophils and monocytes release a soluble form of TNF-related apoptosis-inducing ligand (TRAIL/Apo-2 ligand) displaying apoptotic activity on leukemic cells. Blood 103, 38373844.
58. Zula, J. A., Green, H. C., Ransohoff, R. M., Rudick, R. A., Stark, G. R., van Boxel-Dezaire, A. H. (2011) The role of cell type-specific responses in IFN-β therapy of multiple sclerosis. Proc. Natl. Acad. Sci. USA 108, 19689-19694.
59. Hebb, A. L., Moore, C. S., Bhan, V., Robertson, G. S. (2010) Effects of IFN-β on TRAIL and decoy receptor expression in different immune cell populations from MS patients with distinct disease subtypes. Autoimmune Dis. 2011, 485752.
60. Bustamante, M. F., Fissolo, N., Rio, J., Espejo, C., Costa, C., Mansilla, M. J., Lizasoain, I., Moro, M. A., Carmen Edo, M., Montalban, X., Co-mabella, M. (2011) Implication of the Toll-like receptor 4 pathway in the response to interferon-β in multiple sclerosis. Ann. Neurol. 70, 634645.
61. Comabella, M., Lunemann, J. D., Rio, J., Sanchez, A., Lopez, C., Julia, E., Fernandez, M., Nonell, L., Camina-Tato, M., Deisenhammer, F., Caballero, E., Tortola, M. T., Prinz, M., Montalban, X., Martin, R. (2009) A type I interferon signature in monocytes is associated with poor response to interferon-β in multiple sclerosis. Brain 132, 3353-3365.
62. Van Boxel-Dezaire, A. H., Zula, J. A., Xu, Y., Ransohoff, R. M., Jacob-berger, J. W., Stark, G. R. (2010) Major differences in the responses of primary human leukocyte subsets to IFN-β. J. Immunol. 185, 5888-5899.
63. Dinarello, C. A. (2011) Interleukin-1 in the pathogenesis and treatment of inflammatory diseases. Blood 117, 3720-3732.
64. Brosnan, C. F., Cannella, B., Battistini, L., Raine, C. S. (1995) Cytokine localization in multiple sclerosis lesions: correlation with adhesion molecule expression and reactive nitrogen species. Neurology 45, S16-S21.
65. Martinon, F., Mayor, A., Tschopp, J. (2009) The inflammasomes: guardians of the body. Annu. Rev. Immunol. 27, 229-265.
66. Gris, D., Ye, Z., Iocca, H. A., Wen, H., Craven, R. R., Gris, P., Huang, M., Schneider, M., Miller, S. D., Ting, J. P. (2010) NLRP3 plays a critical role in the development of experimental autoimmune encephalomyelitis by mediating Th1 and Th17 responses. J. Immunol. 185, 974-981.
67. Shaw, P. J., Lukens, J. R., Burns, S., Chi, H., McGargill, M. A., Kanneganti, T. D. (2010) Cutting edge: critical role for PYCARD/ASC in the development of experimental autoimmune encephalomyelitis. J. Immunol. 184, 4610-4614.
68. Henry, T., Brotcke, A., Weiss, D. S., Thompson, L. J., Monack, D. M. (2007) Type I interferon signaling is required for activation of the in-flammasome during Francisella infection. J. Exp. Med. 204, 987-994.
69. Guarda, G., Braun, M., Staehli, F., Tardivel, A., Mattmann, C., Forster, I., Farlik, M., Decker, T., Du Pasquier, R. A., Romero, P., Tschopp, J. (2011) Type I interferon inhibits interleukin-1 production and inflam-masome activation. Immunity 34, 213-223.
70. Veeranki, S., Duan, X., Panchanathan, R., Liu, H., Choubey, D. (2011) IFI16 protein mediates the anti-inflammatory actions of the type-I interferons through suppression of activation of caspase-1 by inflammasomes. PLoS One 6, e27040.
71. Furlan, R., Martino, G., Galbiati, F., Poliani, P. L., Smiroldo, S., Ber-gami, A., Desina, G., Comi, G., Flavell, R., Su, M. S., Adorini, L. (1999) Caspase-1 regulates the inflammatory process leading to autoimmune demyelination. J. Immunol. 163, 2403-2409.
72. Coclet-Ninin, J., Dayer, J. M., Burger, D. (1997) Interferon-β not only inhibits interleukin-^ and tumor necrosis factor-a but stimulates inter leukin-1 receptor antagonist production in human peripheral blood mononuclear cells. Eur. Cytokine Netw. 8, 345-349.
73. Brandt, K J., Carpintero, R., Gruaz, L., Molnarfi, N., Burger, D. (2010) A novel MEK2/PI3K5 pathway controls the expression of IL-1 receptor antagonist in IFN^-activated human monocytes. J. Leukoc. Biol. 88, 1191-1200.
74. Schulz, C., Gomez Perdiguero, E., Chorro, L., Szabo-Rogers, H., Cag-nard, N., Kierdorf, K, Prinz, M., Wu, B., Jacobsen, S.E., Pollard, J.W., Frampton, J., Liu, KJ., Geissmann, F. (2012) A lineage of myeloid cells independent of Myb and hematopoietic stem cells. Science 336, 86-90.
75. Prinz, M., Mildner, A. (2011) Microglia in the CNS: immigrants from another world. Glia 59, 177-187.
76. Ginhoux, F., Greter, M., Leboeuf, M., Nandi, S., See, P., Gokhan, S., Mehler, M. F., Conway, S. J., Ng, L. G., Stanley, E. R., Samokhvalov, I. M., Merad, M. (2010) Fate mapping analysis reveals that adult microglia derive from primitive macrophages. Science 330, 841-845.
77. Ponomarev, E. D., Shriver, L. P., Maresz, K, Dittel, B. N. (2005) Microglial cell activation and proliferation precedes the onset of CNS autoimmunity. J. Neurosci. Res. 81, 374-389.
78. Prinz, M., Priller, J., Sisodia, S. S., Ransohoff, R. M. (2011) Heterogeneity of CNS myeloid cells and their roles in neurodegeneration. Nat. Neu-rosci. 14, 1227-1235.
79. Lassmann, H., Bruck, W., Lucchinetti, C. (2001) Heterogeneity of multiple sclerosis pathogenesis: implications for diagnosis and therapy. Trends Mol. Med. 7, 115-121.
80. Heppner, F. L., Greter, M., Marino, D., Falsig, J., Raivich, G., Hov-elmeyer, N., Waisman, A., Rulicke, T., Prinz, M., Priller, J., Becher, B., Aguzzi, A. (2005) Experimental autoimmune encephalomyelitis repressed by microglial paralysis. Nat. Med. 11, 146-152.
81. Defaux, A., Zurich, M. G., Honegger, P., Monnet-Tschudi, F. (2011) Minocycline promotes remyelination in aggregating rat brain cell cultures after interferon-γ plus lipopolysaccharide-induced demyelination. Neuroscience 187, 84-92.
82. Ponomarev, E. D., Veremeyko, T., Barteneva, N., Krichevsky, A. M., Weiner, H. L. (2011) MicroRNA-124 promotes microglia quiescence and suppresses EAE by deactivating macrophages via the C/EBP-a-PU. 1 pathway. Nat. Med. 17, 64-70.
83. Gao, Z., Tsirka, S. E. (2011) Animal models of MS reveal multiple roles of microglia in disease pathogenesis. Neurol. Res. Int. 2011, 383087.
84. Teige, I., Liu, Y., Issazadeh-Navikas, S. (2006) IFN-β inhibits T cell activation capacity of central nervous system APCs. J. Immunol. 177, 35423553.
85. Kawanokuchi, J., Mizuno, T., Kato, H., Mitsuma, N., Suzumura, A. (2004) Effects of interferon-β on microglial functions as inflammatory and antigen presenting cells in the central nervous system. Neuropharmacology 46, 734-742.
86. Jin, S., Kawanokuchi, J., Mizuno, T., Wang, J., Sonobe, Y., Takeuchi, H., Suzumura, A. (2007) Interferon-β is neuroprotective against the toxicity induced by activated microglia. Brain Res. 1179, 140-146.
87. Kim, M. O., Si, Q., Zhou, J. N., Pestell, R. G., Brosnan, C. F., Locker, J., Lee, S. C. (2002) Interferon-β activates multiple signaling cascades in primary human microglia. J. Neurochem. 81, 1361-1371.
88. Chan, A., Seguin, R., Magnus, T., Papadimitriou, C., Toyka, K V., Antel, J. P., Gold, R. (2003) Phagocytosis of apoptotic inflammatory cells by microglia and its therapeutic implications: termination of CNS autoimmune inflammation and modulation by interferon-β. Glia 43, 231-242.
89. Huizinga, R., van der Star, B. J., Kipp, M., Jong, R., Gerritsen, W., Clarner, T., Puentes, F., Dijkstra, C. D., van der Valk, P., Amor, S. (2012) Phagocytosis of neuronal debris by microglia is associated with neuronal damage in multiple sclerosis. Glia 60, 422-431.