Anti-inflammatory mechanisms of IFN-γ studied in experimental autoimmune encephalomyelitis reveal neutrophils as a potential target in multiple sclerosis

Frontiers in Neuroscience

Volumn 9, Issue JUL, 2015, Pages

  Miller, Nichole M ^a   Wang, Jun ^a,b   Tan, Yanping ^a   Dittel, Bonnie N ^a  

^a BLOOD RESEARCH INSTITUTE   (United States)

^b FUDAN UNIVERSITY   (China)

Author keywords

Anti inflammatory; Experimental autoimmune encephalomyelitis; IFN ; Multiple sclerosis; Neutrophils

Indexed keywords

CD11B ANTIGEN; CD4 ANTIGEN; CHEMOKINE; CXCL1 CHEMOKINE; CXCL11 CHEMOKINE; CXCL9 CHEMOKINE; EPITHELIAL DERIVED NEUTROPHIL ACTIVATING FACTOR 78; GAMMA INTERFERON; GAMMA INTERFERON INDUCIBLE PROTEIN 10; GAMMA INTERFERON RECEPTOR; GLIAL FIBRILLARY ACIDIC PROTEIN; INTERLEUKIN 17; INTERLEUKIN 8; LENTIVIRUS VECTOR; MONOCYTE CHEMOTACTIC PROTEIN 1; NATALIZUMAB; REACTIVE OXYGEN METABOLITE; SHORT HAIRPIN RNA;

ADOPTIVE TRANSFER; ANTIINFLAMMATORY ACTIVITY; APOPTOSIS; ARTICLE; AUTOIMMUNE DISEASE; BLOOD BRAIN BARRIER; CD4+ T LYMPHOCYTE; CENTRAL NERVOUS SYSTEM; CLINICAL TRIAL (TOPIC); CYTOKINE PRODUCTION; DEMYELINATION; DISEASE COURSE; DISEASE EXACERBATION; DISEASE MODEL; DOSAGE SCHEDULE COMPARISON; DRUG TARGETING; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; GENE SILENCING; HUMAN; IMMUNOREGULATION; INHIBITION KINETICS; MORBIDITY; MORTALITY; MULTIPLE SCLEROSIS; NERVE CELL LESION; NEUTROPHIL CHEMOTAXIS; NONHUMAN; PATHOGENESIS; PROTEIN EXPRESSION; REGULATORY T LYMPHOCYTE; RELAPSE; SINGLE DRUG DOSE; TH1 CELL; TH17 CELL;

EID: 84938305062     PISSN: 16624548     EISSN: 1662453X     Source Type: Journal    
DOI: 10.3389/fnins.2015.00287     Document Type: Article

References (126)

1. Abromson-Leeman, S., R. Bronson, Y. Luo, M. Berman, R. Leeman, J. Leeman and M. Dorf (2004). "T-cell properties determine disease site, clinical presentation, and cellular pathology of experimental autoimmune encephalomyelitis". Am J Pathol 165(5): 1519-1533.
2. Akdis, M., S. Burgler, R. Crameri, T. Eiwegger, H. Fujita, E. Gomez, S. Klunker, N. Meyer, L. O'Mahony, O. Palomares, C. Rhyner, N. Ouaked, A. Schaffartzik, W. Van De Veen, S. Zeller, M. Zimmermann and C. A. Akdis (2011). "Interleukins, from 1 to 37, and interferon-gamma: receptors, functions, and roles in diseases". J Allergy Clin Immunol 127(3): 701-721 e701-770.
3. Anderson, C. F., M. Oukka, V. J. Kuchroo and D. Sacks (2007). "CD4(+)CD25(-)Foxp3(-) Th1 cells are the source of IL-10-mediated immune suppression in chronic cutaneous leishmaniasis". J Exp Med 204(2): 285-297.
4. Apetoh, L., F. J. Quintana, C. Pot, N. Joller, S. Xiao, D. Kumar, E. J. Burns, D. H. Sherr, H. L. Weiner and V. K. Kuchroo (2010). "The aryl hydrocarbon receptor interacts with c-Maf to promote the differentiation of type 1 regulatory T cells induced by IL-27". Nat Immunol 11(9): 854-861.
5. Aube, B., S. A. Levesque, A. Pare, E. Chamma, H. Kebir, R. Gorina, M. A. Lecuyer, J. I. Alvarez, Y. De Koninck, B. Engelhardt, A. Prat, D. Cote and S. Lacroix (2014). "Neutrophils mediate blood-spinal cord barrier disruption in demyelinating neuroinflammatory diseases". J Immunol 193(5): 2438-2454.
6. Baron, J. L., J. A. Madri, N. H. Ruddle, G. Hashim and C. A. Janeway, Jr. (1993). "Surface expression of alpha 4 integrin by CD4 T cells is required for their entry into brain parenchyma". J Exp Med 177(1): 57-68.
7. Bennett, C. L., J. Christie, F. Ramsdell, M. E. Brunkow, P. J. Ferguson, L. Whitesell, T. E. Kelly, F. T. Saulsbury, P. F. Chance and H. D. Ochs (2001). "The immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome (IPEX) is caused by mutations of FOXP3". Nat Genet 27(1): 20-21.
8. Berghmans, N., A. Nuyts, C. Uyttenhove, J. Van Snick, G. Opdenakker and H. Heremans (2011). "Interferon gamma orchestrates the number and function of Th17 cells in experimental autoimmune encephalomyelitis". J Interferon Cytokine Res 31(7): 575-587.
9. Bettelli, E., M. P. Das, E. D. Howard, H. L. Weiner, R. A. Sobel and V. K. Kuchroo (1998). "IL-10 is critical in the regulation of autoimmune encephalomyelitis as demonstrated by studies of IL-10-and IL-4-deficient and transgenic mice". J Immunol 161(7): 3299-3306.
10. Billiau, A., H. Heremans, F. Vandekerckhove, R. Dijkmans, H. Sobis, E. Meulepas and H. Carton (1988). "Enhancement of experimental allergic encephalomyelitis in mice by antibodies against IFN-gamma". J Immunol 140(5): 1506-1510.
11. Billiau, A. and P. Matthys (2009). "Interferon-gamma: a historical perspective". Cytokine Growth Factor Rev 20(2): 97-113.
12. Brunkow, M. E., E. W. Jeffery, K. A. Hjerrild, B. Paeper, L. B. Clark, S. A. Yasayko, J. E. Wilkinson, D. Galas, S. F. Ziegler and F. Ramsdell (2001). "Disruption of a new forkhead/winged-helix protein, scurfin, results in the fatal lymphoproliferative disorder of the scurfy mouse". Nat Genet 27(1): 68-73.
13. Byrne, F. R., A. Winters, D. Brankow, S. Hu, T. Juan, S. Steavenson, G. Doellgast, K. Kuchimanchi, H. Brown, S. Anderson, S. Smelt, T. Sullivan, D. Alcorn, J. Tocker, C. Dean, Jr., J. Macmaster, J. Kirchner, J. Buys, R. Manoukian, E. Jiao, X. Zou, G. S. Campanella and G. Siu (2009). "An antibody to IP-10 is a potent antagonist of cell migration in vitro and in vivo and does not affect disease in several animal models of inflammation". Autoimmunity 42(3): 171-182.
14. Carlson, T., M. Kroenke, P. Rao, T. E. Lane and B. Segal (2008). "The Th17-ELR+ CXC chemokine pathway is essential for the development of central nervous system autoimmune disease". J Exp Med 205(4): 811-823.
15. Carter, S. L., M. Muller, P. M. Manders and I. L. Campbell (2007). "Induction of the genes for Cxcl9 and Cxcl10 is dependent on IFN-gamma but shows differential cellular expression in experimental autoimmune encephalomyelitis and by astrocytes and microglia in vitro". Glia 55(16): 1728-1739.
16. Chen, W., W. Jin, N. Hardegen, K. J. Lei, L. Li, N. Marinos, G. McGrady and S. M. Wahl (2003). "Conversion of peripheral CD4+CD25-naive T cells to CD4+CD25+ regulatory T cells by TGF-beta induction of transcription factor Foxp3". J Exp Med 198(12): 1875-1886.
17. Chin, Y. E., M. Kitagawa, K. Kuida, R. A. Flavell and X. Y. Fu (1997). "Activation of the STAT signaling pathway can cause expression of caspase 1 and apoptosis". Mol Cell Biol 17(9): 5328-5337.
18. Christy, A. L., M. E. Walker, M. J. Hessner and M. A. Brown (2013). "Mast cell activation and neutrophil recruitment promotes early and robust inflammation in the meninges in EAE". J Autoimmun 42: 50-61.
19. Chu, C. Q., S. Wittmer and D. K. Dalton (2000). "Failure to suppress the expansion of the activated CD4 T cell population in interferon gamma-deficient mice leads to exacerbation of experimental autoimmune encephalomyelitis". J Exp Med 192(1): 123-128.
20. Chung, Y., S. H. Chang, G. J. Martinez, X. O. Yang, R. Nurieva, H. S. Kang, L. Ma, S. S. Watowich, A. M. Jetten, Q. Tian and C. Dong (2009). "Critical regulation of early Th17 cell differentiation by interleukin-1 signaling". Immunity 30(4): 576-587.
21. Committee, N. I. o. H. A. C. (2002). "Autoimmune Diseases Research Plan". NIH Publication No. 03-5140.
22. Cross, A. H., T. O'Mara and C. S. Raine (1993). "Chronologic localization of myelin-reactive cells in the lesions of relapsing EAE: implications for the study of multiple sclerosis". Neurology 43(5): 1028-1033.
23. Dalton, D. K., S. Pitts-Meek, S. Keshav, I. S. Figari, A. Bradley and T. A. Stewart (1993). "Multiple defects of immune cell function in mice with disrupted interferon-gamma genes". Science 259(5102): 1739-1742.
24. Davidson, T. S., R. J. DiPaolo, J. Andersson and E. M. Shevach (2007). "Cutting Edge: IL-2 is essential for TGF-beta-mediated induction of Foxp3+ T regulatory cells". J Immunol 178(7): 4022-4026.
25. Demirci, S., S. Demirci, S. Kutluhan, H. R. Koyuncuoglu and V. A. Yurekli (2015). "The Clinical Significance of the Neutrophil-to-Lymphocyte Ratio in Multiple Sclerosis". Int J Neurosci: 1-24.
26. Ding, X., Y. Yan, X. Li, K. Li, B. Ciric, J. Yang, Y. Zhang, S. Wu, H. Xu, W. Chen, A. E. Lovett-Racke, G. X. Zhang and A. Rostami (2015). "Silencing IFN-gamma Binding/Signaling in Astrocytes versus Microglia Leads to Opposite Effects on Central Nervous System Autoimmunity". J Immunol 194(9): 4251-4264.
27. Dittel, B. N. (2000). "Evidence that Fas and FasL contribute to the pathogenesis of experimental autoimmune encephalomyelitis". Arch Immunol Ther Exp (Warsz) 48(5): 381-388.
28. Dittel, B. N. (2008). "CD4 T cells: Balancing the coming and going of autoimmune-mediated inflammation in the CNS". Brain Behav Immun 22(4): 421-430.
29. Dittel, B. N., R. M. Merchant and C. A. Janeway, Jr. (1999). "Evidence for Fas-dependent and Fas-independent mechanisms in the pathogenesis of experimental autoimmune encephalomyelitis". J Immunol 162(11): 6392-6400.
30. Diveu, C., M. J. McGeachy, K. Boniface, J. S. Stumhofer, M. Sathe, B. Joyce-Shaikh, Y. Chen, C. M. Tato, T. K. McClanahan, R. de Waal Malefyt, C. A. Hunter, D. J. Cua and R. A. Kastelein (2009). "IL-27 blocks RORc expression to inhibit lineage commitment of Th17 cells". J Immunol 182(9): 5748-5756.
31. Duong, T. T., J. St Louis, J. J. Gilbert, F. D. Finkelman and G. H. Strejan (1992). "Effect of anti-interferon gamma and anti-interleukin-2 monoclonal antibody treatment on the development of actively and passively induced experimental allergic encephalomyelitis in the SJL/J mouse". J Neuroimmunol 36(2-3): 105-115.
32. El-Behi, M., B. Ciric, H. Dai, Y. Yan, M. Cullimore, F. Safavi, G. X. Zhang, B. N. Dittel and A. Rostami (2011). "The encephalitogenicity of T(H)17 cells is dependent on IL-1-and IL-23-induced production of the cytokine GM-CSF". Nat Immunol 12(6): 568-575.
33. Ferber, I. A., S. Brocke, C. Taylor-Edwards, W. Ridgway, C. Dinisco, L. Steinman, D. Dalton and C. G. Fathman (1996). "Mice with a disrupted IFN-gamma gene are susceptible to the induction of experimental autoimmune encephalomyelitis (EAE)". J Immunol 156(1): 5-7.
34. Fife, B. T., K. J. Kennedy, M. C. Paniagua, N. W. Lukacs, S. L. Kunkel, A. D. Luster and W. J. Karpus (2001). "CXCL10 (IFN-gamma-inducible protein-10) control of encephalitogenic CD4+ T cell accumulation in the central nervous system during experimental autoimmune encephalomyelitis". J Immunol 166(12): 7617-7624.
35. Fitzgerald, D. C., B. Ciric, T. Touil, H. Harle, J. Grammatikopolou, J. Das Sarma, B. Gran, G. X. Zhang and A. Rostami (2007). "Suppressive effect of IL-27 on encephalitogenic Th17 cells and the effector phase of experimental autoimmune encephalomyelitis". J Immunol 179(5): 3268-3275.
36. Fontenot, J. D., M. A. Gavin and A. Y. Rudensky (2003). "Foxp3 programs the development and function of CD4+CD25+ regulatory T cells". Nat Immunol 4(4): 330-336.
37. Geissmann, F., S. Jung and D. R. Littman (2003). "Blood monocytes consist of two principal subsets with distinct migratory properties". Immunity 19(1): 71-82.
38. Gilgun-Sherki, Y., E. Melamed and D. Offen (2004). "The role of oxidative stress in the pathogenesis of multiple sclerosis: the need for effective antioxidant therapy". J Neurol 251(3): 261-268.
39. Glabinski, A. R., M. Krakowski, Y. Han, T. Owens and R. M. Ransohoff (1999). "Chemokine expression in GKO mice (lacking interferon-gamma) with experimental autoimmune encephalomyelitis". J Neurovirol 5(1): 95-101.
40. Goverman, J., A. Woods, L. Larson, L. P. Weiner, L. Hood and D. M. Zaller (1993). "Transgenic mice that express a myelin basic protein-specific T cell receptor develop spontaneous autoimmunity". Cell 72(4): 551-560.
41. Gran, B., N. Chu, G. X. Zhang, S. Yu, Y. Li, X. H. Chen, M. Kamoun and A. Rostami (2004). "Early administration of IL-12 suppresses EAE through induction of interferon-gamma". J Neuroimmunol 156(1-2): 123-131.
42. Gultner, S., T. Kuhlmann, A. Hesse, J. P. Weber, C. Riemer, M. Baier and A. Hutloff (2010). "Reduced Treg frequency in LFA-1-deficient mice allows enhanced T effector differentiation and pathology in EAE". Eur J Immunol 40(12): 3403-3412.
43. Hall, A. O., D. P. Beiting, C. Tato, B. John, G. Oldenhove, C. G. Lombana, G. H. Pritchard, J. S. Silver, N. Bouladoux, J. S. Stumhofer, T. H. Harris, J. Grainger, E. D. Wojno, S. Wagage, D. S. Roos, P. Scott, L. A. Turka, S. Cherry, S. L. Reiner, D. Cua, Y. Belkaid, M. M. Elloso and C. A. Hunter (2012). "The cytokines interleukin 27 and interferon-gamma promote distinct Treg cell populations required to limit infection-induced pathology". Immunity 37(3): 511-523.
44. Harrington, L. E., R. D. Hatton, P. R. Mangan, H. Turner, T. L. Murphy, K. M. Murphy and C. T. Weaver (2005). "Interleukin 17-producing CD4+ effector T cells develop via a lineage distinct from the T helper type 1 and 2 lineages". Nat Immunol 6(11): 1123-1132.
45. Hindinger, C., C. C. Bergmann, D. R. Hinton, T. W. Phares, G. I. Parra, S. Hussain, C. Savarin, R. D. Atkinson and S. A. Stohlman (2012). "IFN-gamma signaling to astrocytes protects from autoimmune mediated neurological disability". PLoS One 7(7): e42088.
46. Hindinger, C., J. M. Gonzalez, C. C. Bergmann, B. Fuss, D. R. Hinton, R. D. Atkinson, W. B. Macklin and S. A. Stohlman (2005). "Astrocyte expression of a dominant-negative interferon-gamma receptor". J Neurosci Res 82(1): 20-31.
47. Hori, S., T. Nomura and S. Sakaguchi (2003). "Control of regulatory T cell development by the transcription factor Foxp3". Science 299(5609): 1057-1061.
48. Hovelmeyer, N., Z. Hao, K. Kranidioti, G. Kassiotis, T. Buch, F. Frommer, L. von Hoch, D. Kramer, L. Minichiello, G. Kollias, H. Lassmann and A. Waisman (2005). "Apoptosis of oligodendrocytes via Fas and TNF-R1 is a key event in the induction of experimental autoimmune encephalomyelitis". J Immunol 175(9): 5875-5884.
49. Huang, S., W. Hendriks, A. Althage, S. Hemmi, H. Bluethmann, R. Kamijo, J. Vilcek, R. M. Zinkernagel and M. Aguet (1993). "Immune response in mice that lack the interferon-gamma receptor". Science 259(5102): 1742-1745.
50. Inoue, M., K. L. Williams, M. D. Gunn and M. L. Shinohara (2012). "NLRP3 inflammasome induces chemotactic immune cell migration to the CNS in experimental autoimmune encephalomyelitis". Proc Natl Acad Sci U S A 109(26): 10480-10485.
51. Iwakura, Y., H. Ishigame, S. Saijo and S. Nakae (2011). "Functional specialization of interleukin-17 family members". Immunity 34(2): 149-162.
52. Jadidi-Niaragh, F. and A. Mirshafiey (2011). "Th17 cell, the new player of neuroinflammatory process in multiple sclerosis". Scand J Immunol 74(1): 1-13.
53. Jankovic, D., M. C. Kullberg, C. G. Feng, R. S. Goldszmid, C. M. Collazo, M. Wilson, T. A. Wynn, M. Kamanaka, R. A. Flavell and A. Sher (2007). "Conventional T-bet(+)Foxp3(-) Th1 cells are the major source of host-protective regulatory IL-10 during intracellular protozoan infection". J Exp Med 204(2): 273-283.
54. Kanayama, M., M. Inoue, K. Danzaki, G. Hammer, Y. W. He and M. L. Shinohara (2015). "Autophagy enhances NFkappaB activity in specific tissue macrophages by sequestering A20 to boost antifungal immunity". Nat Commun 6: 5779.
55. Kang, Z., C. Z. Altuntas, M. F. Gulen, C. Liu, N. Giltiay, H. Qin, L. Liu, W. Qian, R. M. Ransohoff, C. Bergmann, S. Stohlman, V. K. Tuohy and X. Li (2010). "Astrocyte-restricted ablation of interleukin-17-induced Act1-mediated signaling ameliorates autoimmune encephalomyelitis". Immunity 32(3): 414-425.
56. Kang, Z., C. Wang, J. Zepp, L. Wu, K. Sun, J. Zhao, U. Chandrasekharan, P. E. DiCorleto, B. D. Trapp, R. M. Ransohoff and X. Li (2013). "Act1 mediates IL-17-induced EAE pathogenesis selectively in NG2+ glial cells". Nat Neurosci 16(10): 1401-1408.
57. Karpus, W. J. and R. M. Ransohoff (1998). "Chemokine regulation of experimental autoimmune encephalomyelitis: temporal and spatial expression patterns govern disease pathogenesis". J Immunol 161(6): 2667-2671.
58. Kasper, S., T. Kindler, S. Sonnenschein, F. Breitenbuecher, F. D. Bohmer, C. Huber and T. Fischer (2007). "Cross-inhibition of interferon-induced signals by GM-CSF through a block in Stat1 activation". J Interferon Cytokine Res 27(11): 947-959.
59. Kelchtermans, H., A. Billiau and P. Matthys (2008). "How interferon-gamma keeps autoimmune diseases in check". Trends Immunol 29(10): 479-486.
60. Kelchtermans, H., B. De Klerck, T. Mitera, M. Van Balen, D. Bullens, A. Billiau, G. Leclercq and P. Matthys (2005). "Defective CD4+CD25+ regulatory T cell functioning in collagen-induced arthritis: an important factor in pathogenesis, counter-regulated by endogenous IFN-gamma". Arthritis Res Ther 7(2): R402-415.
61. Klein, R. S., L. Izikson, T. Means, H. D. Gibson, E. Lin, R. A. Sobel, H. L. Weiner and A. D. Luster (2004). "IFN-inducible protein 10/CXC chemokine ligand 10-independent induction of experimental autoimmune encephalomyelitis". J Immunol 172(1): 550-559.
62. Kohler, R. E., I. Comerford, S. Townley, S. Haylock-Jacobs, I. Clark-Lewis and S. R. McColl (2008). "Antagonism of the chemokine receptors CXCR3 and CXCR4 reduces the pathology of experimental autoimmune encephalomyelitis". Brain Pathol 18(4): 504-516.
63. Kohm, A. P., P. A. Carpentier, H. A. Anger and S. D. Miller (2002). "Cutting edge: CD4+CD25+ regulatory T cells suppress antigen-specific autoreactive immune responses and central nervous system inflammation during active experimental autoimmune encephalomyelitis". J Immunol 169(9): 4712-4716.
64. Komiyama, Y., S. Nakae, T. Matsuki, A. Nambu, H. Ishigame, S. Kakuta, K. Sudo and Y. Iwakura (2006). "IL-17 plays an important role in the development of experimental autoimmune encephalomyelitis". J Immunol 177(1): 566-573.
65. Kozuka, T., K. Kojima, K. Kaneda, K. Takenaka, Y. Manabe, Y. Hirata, S. Okuma, H. Toki and M. Tanimoto (2003). "Autoimmune neutropenia associated with multiple sclerosis". Intern Med 42(1): 102-104.
66. Krakowski, M. and T. Owens (1996). "Interferon-gamma confers resistance to experimental allergic encephalomyelitis". Eur J Immunol 26(7): 1641-1646.
67. Kroenke, M. A., T. J. Carlson, A. V. Andjelkovic and B. M. Segal (2008). "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 205(7): 1535-1541.
68. Kwidzinski, E., J. Bunse, A. D. Kovac, O. Ullrich, F. Zipp, R. Nitsch and I. Bechmann (2003). "IDO (indolamine 2,3-dioxygenase) expression and function in the CNS". Adv Exp Med Biol 527: 113-118.
69. Lalor, S. J., L. S. Dungan, C. E. Sutton, S. A. Basdeo, J. M. Fletcher and K. H. Mills (2011). "Caspase-1-processed cytokines IL-1beta and IL-18 promote IL-17 production by gammadelta and CD4 T cells that mediate autoimmunity". J Immunol 186(10): 5738-5748.
70. Lalor, S. J. and B. M. Segal (2013). "Th1-mediated experimental autoimmune encephalomyelitis is CXCR3 independent". Eur J Immunol 43(11): 2866-2874.
71. Lee, E., S. Chanamara, D. Pleasure and A. M. Soulika (2012). "IFN-gamma signaling in the central nervous system controls the course of experimental autoimmune encephalomyelitis independently of the localization and composition of inflammatory foci". J Neuroinflammation 9: 7.
72. Lees, J. R., P. T. Golumbek, J. Sim, D. Dorsey and J. H. Russell (2008). "Regional CNS responses to IFN gamma determine lesion localization patterns during EAE pathogenesis". J Exp Med 205(11): 2633-2642.
73. Liu, L., D. Huang, M. Matsui, T. T. He, T. Hu, J. Demartino, B. Lu, C. Gerard and R. M. Ransohoff (2006). "Severe disease, unaltered leukocyte migration, and reduced IFN-gamma production in CXCR3-/-mice with experimental autoimmune encephalomyelitis". J Immunol 176(7): 4399-4409.
74. Liu, Y. and C. A. Janeway, Jr. (1990). "Interferon gamma plays a critical role in induced cell death of effector T cell: a possible third mechanism of self-tolerance". J Exp Med 172(6): 1735-1739.
75. Loda, E. and R. Balabanov (2012). "Interferon regulatory factor 1 re gulation of oligodendrocyte injury and inflammatory demyelination". Rev Neurosci 23(2): 145-152.
76. Lovett-Racke, A. E., Y. Yang and M. K. Racke (2011). "Th1 versus Th17: are T cell cytokines relevant in multiple sclerosis?". Biochim Biophys Acta 1812(2): 246-251.
77. Lund, B. T., N. Ashikian, H. Q. Ta, Y. Chakryan, K. Manoukian, S. Groshen, W. Gilmore, G. S. Cheema, W. Stohl, M. E. Burnett, D. Ko, N. J. Kachuck and L. P. Weiner (2004). "Increased CXCL8 (IL-8) expression in Multiple Sclerosis". J Neuroimmunol 155(1-2): 161-171.
78. McCarthy, D. P., M. H. Richards and S. D. Miller (2012). "Mouse models of multiple sclerosis: experimental autoimmune encephalomyelitis and Theiler's virus-induced demyelinating disease". Methods Mol Biol 900: 381-401.
79. McColl, S. R., M. A. Staykova, A. Wozniak, S. Fordham, J. Bruce and D. O. Willenborg (1998). "Treatment with anti-granulocyte antibodies inhibits the effector phase of experimental autoimmune encephalomyelitis". J Immunol 161(11): 6421-6426.
80. McGeachy, M. J., L. A. Stephens and S. M. Anderton (2005). "Natural Recovery and Protection from Autoimmune Encephalomyelitis: Contribution of CD4+CD25+ Regulatory Cells within the Central Nervous System". J Immunol 175(5): 3025-3032.
81. Mellor, A. L. and D. H. Munn (2004). "IDO expression by dendritic cells: tolerance and tryptophan catabolism". Nat Rev Immunol 4(10): 762-774.
82. Muller, M., S. L. Carter, M. J. Hofer, P. Manders, D. R. Getts, M. T. Getts, A. Dreykluft, B. Lu, C. Gerard, N. J. King and I. L. Campbell (2007). "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 179(5): 2774-2786.
83. Munzel, E. J., J. Z. Wimperis and A. Williams (2013). "Relapsing-remitting multiple sclerosis and chronic idiopathic neutropenia: a challenging combination". BMJ Case Rep 2013.
84. Naegele, M., K. Tillack, S. Reinhardt, S. Schippling, R. Martin and M. Sospedra (2012). "Neutrophils in multiple sclerosis are characterized by a primed phenotype". J Neuroimmunol 242(1-2): 60-71.
85. Narumi, S., T. Kaburaki, H. Yoneyama, H. Iwamura, Y. Kobayashi and K. Matsushima (2002). "Neutralization of IFN-inducible protein 10/CXCL10 exacerbates experimental autoimmune encephalomyelitis". Eur J Immunol 32(6): 1784-1791.
86. Neighbour, P. A., A. E. Miller and B. R. Bloom (1981). "Interferon responses of leukocytes in multiple sclerosis". Neurology 31(5): 561-566.
87. Nylander, A. and D. A. Hafler (2012). "Multiple sclerosis". J Clin Invest 122(4): 1180-1188.
88. Panitch, H. S. (1994). "Influence of infection on exacerbations of multiple sclerosis". Ann Neurol 36 Suppl: S25-28.
89. Panitch, H. S., R. L. Hirsch, A. S. Haley and K. P. Johnson (1987). "Exacerbations of multiple sclerosis in patients treated with gamma interferon". Lancet 1(8538): 893-895.
90. Park, H., Z. Li, X. O. Yang, S. H. Chang, R. Nurieva, Y. H. Wang, Y. Wang, L. Hood, Z. Zhu, Q. Tian and C. Dong (2005). "A distinct lineage of CD4 T cells regulates tissue inflammation by producing interleukin 17". Nat Immunol 6(11): 1133-1141.
91. Platanias, L. C. (2005). "Mechanisms of type-I-and type-II-interferon-mediated signalling". Nat Rev Immunol 5(5): 375-386.
92. Podikoglou, D. G., P. E. Lianou, C. D. Tsakanikas and J. T. Papavassiliou (1994). "Polymorphonuclear leukocyte functions and multiple sclerosis". Neurology 44(1): 129-132.
93. Ponomarev, E. D., K. Maresz, Y. Tan and B. N. Dittel (2007). "CNS-derived interleukin-4 is essential for the regulation of autoimmune inflammation and induces a state of alternative activation in microglial cells". J Neurosci 27(40): 10714-10721.
94. Ponomarev, E. D., L. P. Shriver, K. Maresz and B. N. Dittel (2005). "Microglial cell activation and proliferation precedes the onset of CNS autoimmunity". J Neurosci Res 81(3): 374-389.
95. Ponomarev, E. D., L. P. Shriver, K. Maresz, J. Pedras-Vasconcelos, D. Verthelyi and B. N. Dittel (2007). "GM CSF production by autoreactive T cells is required for the activation of microglial cells and the onset of experimental autoimmune encephalomyelitis". J Immunol 178(1): 39-48.
96. Ramana, C. V., M. P. Gil, R. D. Schreiber and G. R. Stark (2002). "Stat1-dependent and-independent pathways in IFN-gamma-dependent signaling". Trends Immunol 23(2): 96-101.
97. Ray, A., S. Basu, C. B. Williams, N. H. Salzman and B. N. Dittel (2012). "A novel IL-10-independent regulatory role for B cells in suppressing autoimmunity by maintenance of regulatory T cells via GITR ligand". J Immunol 188(7): 3188-3198.
98. Ren, Z., Y. Wang, D. Liebenson, T. Liggett, R. Goswami, D. Stefoski and R. Balabanov (2011). "IRF-1 signaling in central nervous system glial cells regulates inflammatory demyelination". J Neuroimmunol 233(1-2): 147-159.
99. Rumble, J. M., A. K. Huber, G. Krishnamoorthy, A. Srinivasan, D. A. Giles, X. Zhang, L. Wang and B. M. Segal (2015). "Neutrophil-related factors as biomarkers in EAE and MS". J Exp Med 212(1): 23-35.
100. Sabelko-Downes, K. A., A. H. Cross and J. H. Russell (1999). "Dual role for Fas ligand in the initiation of and recovery from experimental allergic encephalomyelitis". J Exp Med 189(8): 1195-1205.
101. Saha, B., S. Jyothi Prasanna, B. Chandrasekar and D. Nandi (2010). "Gene modulation and immunoregulatory roles of interferon gamma". Cytokine 50(1): 1-14.
102. Sakurai, K., J. P. Zou, J. R. Tschetter, J. M. Ward and G. M. Shearer (2002). "Effect of indoleamine 2,3-dioxygenase on induction of experimental autoimmune encephalomyelitis". J Neuroimmunol 129(1-2): 186-196.
103. Sallusto, F., D. Lenig, C. R. Mackay and A. Lanzavecchia (1998). "Flexible programs of chemokine receptor expression on human polarized T helper 1 and 2 lymphocytes". J Exp Med 187(6): 875-883.
104. Shiomi, A. and T. Usui (2015). "Pivotal roles of GM-CSF in autoimmunity and inflammation". Mediators Inflamm 2015: 568543.
105. Shriver, L. P. and B. N. Dittel (2006). "T-cell-mediated disruption of the neuronal microtubule network: correlation with early reversible axonal dysfunction in acute experimental autoimmune encephalomyelitis". Am J Pathol 169(3): 999-1011.
106. Simmons, S. B., D. Liggitt and J. M. Goverman (2014). "Cytokine-regulated neutrophil recruitment is required for brain but not spinal cord inflammation during experimental autoimmune encephalomyelitis". J Immunol 193(2): 555-563.
107. Steinbach, K., M. Piedavent, S. Bauer, J. T. Neumann and M. A. Friese (2013). "Neutrophils amplify autoimmune central nervous system infiltrates by maturing local APCs". J Immunol 191(9): 4531-4539.
108. Stoolman, J. S., P. C. Duncker, A. K. Huber and B. M. Segal (2014). "Site-specific chemokine expression regulates central nervous system inflammation and determines clinical phenotype in autoimmune encephalomyelitis". J Immunol 193(2): 564-570.
109. Stromnes, I. M., L. M. Cerretti, D. Liggitt, R. A. Harris and J. M. Goverman (2008). "Differential regulation of central nervous system autoimmunity by T(H)1 and T(H)17 cells". Nat Med 14(3): 337-342.
110. Sweeney, C. M., R. Lonergan, S. A. Basdeo, K. Kinsella, L. S. Dungan, S. C. Higgins, P. J. Kelly, L. Costelloe, N. Tubridy, K. H. Mills and J. M. Fletcher (2011). "IL-27 mediates the response to IFN-beta therapy in multiple sclerosis patients by inhibiting Th17 cells". Brain Behav Immun 25(6): 1170-1181.
111. Tran, E. H., E. N. Prince and T. Owens (2000). "IFN-gamma shapes immune invasion of the central nervous system via regulation of chemokines". J Immunol 164(5): 2759-2768.
112. Tsunoda, I., T. E. Lane, J. Blackett and R. S. Fujinami (2004). "Distinct roles for IP-10/CXCL10 in three animal models, Theiler's virus infection, EAE, and MHV infection, for multiple sclerosis: implication of differing roles for IP-10". Mult Scler 10(1): 26-34.
113. Vervliet, G., H. Claeys, H. Van Haver, H. Carton, C. Vermylen, E. Meulepas and A. Billiau (1983). "Interferon production and natural killer (NK) activity in leukocyte cultures from multiple sclerosis patients". J Neurol Sci 60(1): 137-150.
114. Voorthuis, J. A., B. M. Uitdehaag, C. J. De Groot, P. H. Goede, P. H. van der Meide and C. D. Dijkstra (1990). "Suppression of experimental allergic encephalomyelitis by intraventricular administration of interferon-gamma in Lewis rats". Clin Exp Immunol 81(2): 183-188.
115. Wang, Z., J. Hong, W. Sun, G. Xu, N. Li, X. Chen, A. Liu, L. Xu, B. Sun and J. Z. Zhang (2006). "Role of IFN gamma in induction of Foxp3 and conversion of CD4+ CD25-T cells to CD4+ Tregs". J Clin Invest 116(9): 2434-2441.
116. Wensky, A. K., G. C. Furtado, M. C. Marcondes, S. Chen, D. Manfra, S. A. L ira, D. Zagzag and J. J. Lafaille (2005). "IFN-gamma determines distinct clinical outcomes in autoimmune encephalomyelitis". J Immunol 174(3): 1416-1423.
117. Wildin, R. S., F. Ramsdell, J. Peake, F. Faravelli, J. L. Casanova, N. Buist, E. Levy-Lahad, M. Mazzella, O. Goulet, L. Perroni, F. D. Bricarelli, G. Byrne, M. McEuen, S. Proll, M. Appleby and M. E. Brunkow (2001). "X-linked neonatal diabetes mellitus, enteropathy and endocrinopathy syndrome is the human equivalent of mouse scurfy". Nat Genet 27(1): 18-20.
118. Willenborg, D. O., S. Fordham, C. C. Bernard, W. B. Cowden and I. A. Ramshaw (1996). "IFN-gamma plays a critical down-regulatory role in the induction and effector phase of myelin oligodendrocyte glycoprotein induced autoimmune encephalomyelitis". J Immunol 157(8): 3223-3227.
119. Willenborg, D. O., S. A. Fordham, M. A. Staykova, I. A. Ramshaw and W. B. Cowden (1999). "IFN-gamma is critical to the control of murine autoimmune encephalomyelitis and regulates both in the periphery and in the target tissue: a possible role for nitric oxide". J Immunol 163(10): 5278-5286.
120. Xu, X., X. Y. Fu, J. Plate and A. S. Chong (1998). "IFN-gamma induces cell growth inhibition by Fas-mediated apoptosis: requirement of STAT1 protein for up-regulation of Fas and FasL expression". Cancer Res 58(13): 2832-2837.
121. Yan, Y., G. X. Zhang, B. Gran, F. Fallarino, S. Yu, H. Li, M. L. Cullimore, A. Rostami and H. Xu (2010). "IDO upregulates regulatory T cells via tryptophan catabolite and suppresses encephalitogenic T cell responses in experimental autoimmune encephalomyelitis". J Immunol 185(10): 5953-5961.
122. Zehntner, S. P., C. Brickman, L. Bourbonniere, L. Remington, M. Caruso and T. Owens (2005). "Neutrophils that infiltrate the central nervous system regulate T cell responses". J Immunol 174(8): 5124-5131.
123. Zhang, G. X., B. Gran, S. Yu, J. Li, I. Siglienti, X. Chen, M. Kamoun and A. Rostami (2003). "Induction of experimental autoimmune encephalomyelitis in IL-12 receptor-beta 2-deficient mice: IL-12 responsiveness is not required in the pathogenesis of inflammatory demyelination in the central nervous system". J Immunol 170(4): 2153-2160.
124. Zhang, S. Y., S. Boisson-Dupuis, A. Chapgier, K. Yang, J. Bustamante, A. Puel, C. Picard, L. Abel, E. Jouanguy and J. L. Casanova (2008). "Inborn errors of interferon (IFN)-mediated immunity in humans: insights into the respective roles of IFN-alpha/beta, IFN-gamma, and IFN-lambda in host defense". Immunol Rev 226: 29-40.
125. Ziaber, J., J. Pasnik, Z. Baj, L. Pokoca, H. Chmielewski and H. Tchorzewski (1998). "The immunoregulatory abilities of polymorphonuclear neutrophils in the course of multiple sclerosis". Mediators Inflamm 7(5): 335-338.
126. Zohar, Y., G. Wildbaum, R. Novak, A. L. Salzman, M. Thelen, R. Alon, Y. Barsheshet, C. L. Karp and N. Karin (2014). "CXCL11-dependent induction of FOXP3-negative regulatory T cells suppresses autoimmune encephalomyelitis". J Clin Invest 124(5): 2009-2022.