• 1
    Ben-Nun, A., Wekerle, H. and Cohen, I. R., The rapid isolation of clonable antigen-specific T lymphocyte lines capable of mediating autoimmune encephalomyelitis. Eur. J. Immunol. 1981. 11: 195199.
  • 2
    Ferber, I. A., Brocke, S., Taylor-Edwards, C., Ridgway, W., Dinisco, C., Steinman, L., Dalton, D. and Fathman, C. G., Mice with a disrupted IFN-gamma gene are susceptible to the induction of experimental autoimmune encephalomyelitis (EAE). J. Immunol. 1996. 156: 57.
  • 3
    Krakowski, M. and Owens, T., Interferon-gamma confers resistance to experimental allergic encephalomyelitis. Eur. J. Immunol. 1996. 26: 16411646.
  • 4
    Willenborg, D. O., Fordham, S., Bernard, C. C., Cowden, W. B. and Ramshaw, I. A., IFN-gamma plays a critical down-regulatory role in the induction and effector phase of myelin oligodendrocyte glycoprotein-induced autoimmune encephalomyelitis. J. Immunol. 1996. 157: 32233227.
  • 5
    Bettelli, E., Korn, T., Oukka, M. and Kuchroo, V. K., Induction and effector functions of T(H)17 cells. Nature 2008. 453: 10511057.
  • 6
    Sutton, C., Brereton, C., Keogh, B., Mills, K. H. and Lavelle, E. C., A crucial role for interleukin (IL)-1 in the induction of IL-17-producing T cells that mediate autoimmune encephalomyelitis. J. Exp. Med. 2006. 203: 16851691.
  • 7
    Aranami, T. and Yamamura, T., Th17 Cells and autoimmune encephalomyelitis (EAE/MS). Allergol. Int. 2008. 57: 115120.
  • 8
    Hofstetter, H., Gold, R. and Hartung, H. P., Th17 Cells in MS and Experimental Autoimmune Encephalomyelitis. Int. MS J. 2009. 16: 1218.
  • 9
    Zhou, L. and Littman, D. R., Transcriptional regulatory networks in Th17 cell differentiation. Curr. Opin. Immunol. 2009. 21: 146152.
  • 10
    Komiyama, Y., Nakae, S., Matsuki, T., Nambu, A., Ishigame, H., Kakuta, S., Sudo, K. and Iwakura, Y., IL-17 plays an important role in the development of experimental autoimmune encephalomyelitis. J. Immunol. 2006. 177: 566573.
  • 11
    Lock, C., Hermans, G., Pedotti, R., Brendolan, A., Schadt, E., Garren, H., Langer-Gould, A. et al., Gene-microarray analysis of multiple sclerosis lesions yields new targets validated in autoimmune encephalomyelitis. Nat. Med. 2002. 8: 500508.
  • 12
    Ishizu, T., Osoegawa, M., Mei, F. J., Kikuchi, H., Tanaka, M., Takakura, Y., Minohara, M. et al., Intrathecal activation of the IL-17/IL-8 axis in opticospinal multiple sclerosis. Brain 2005. 128: 9881002.
  • 13
    Kebir, H., Kreymborg, K., Ifergan, I., Dodelet-Devillers, A., Cayrol, R., Bernard, M., Giuliani, F. et al., Human TH17 lymphocytes promote blood-brain barrier disruption and central nervous system inflammation. Nat. Med. 2007. 13: 11731175.
  • 14
    Aggarwal, S. and Gurney, A. L., IL-17: prototype member of an emerging cytokine family. J. Leukoc. Biol. 2002. 71: 18.
  • 15
    Ivanov, II, McKenzie, B. S., Zhou, L., Tadokoro, C. E., Lepelley, A., Lafaille, J. J., Cua, D. J. and Littman, D. R., The orphan nuclear receptor RORgammat directs the differentiation program of proinflammatory IL-17+ T helper cells. Cell 2006. 126: 11211133.
  • 16
    Leppkes, M., Becker, C., Ivanov, II, Hirth, S., Wirtz, S., Neufert, C., Pouly, S. et al., RORgamma-expressing Th17 cells induce murine chronic intestinal inflammation via redundant effects of IL-17A and IL-17F. Gastroenterology 2009. 136: 257267.
  • 17
    McGeachy, M. J., Chen, Y., Tato, C. M., Laurence, A., Joyce-Shaikh, B., Blumenschein, W. M., McClanahan, T. K. et al., The interleukin 23 receptor is essential for the terminal differentiation of interleukin 17-producing effector T helper cells in vivo. Nat. Immunol. 2009. 10: 314324.
  • 18
    Elson, C. O., Cong, Y., Weaver, C. T., Schoeb, T. R., McClanahan, T. K., Fick, R. B. and Kastelein, R. A., Monoclonal anti-interleukin 23 reverses active colitis in a T cell-mediated model in mice. Gastroenterology 2007. 132: 23592370.
  • 19
    Feske, S., Giltnane, J., Dolmetsch, R., Staudt, L. M. and Rao, A., Gene regulation mediated by calcium signals in T lymphocytes. Nat. Immunol. 2001. 2: 316324.
  • 20
    Feske, S., Calcium signalling in lymphocyte activation and disease. Nat. Rev. Immunol. 2007. 7: 690702.
  • 21
    Cahalan, M. D., STIMulating store-operated Ca(2+) entry. Nat. Cell Biol. 2009. 11: 669677.
  • 22
    Feske, S., ORAI1 and STIM1 deficiency in human and mice: roles of store-operated Ca2+ entry in the immune system and beyond. Immunol. Rev. 2009. 231: 189209.
  • 23
    Gwack, Y., Srikanth, S., Oh-Hora, M., Hogan, P. G., Lamperti, E. D., Yamashita, M., Gelinas, C. et al., Hair loss and defective T- and B-cell function in mice lacking ORAI1. Mol. Cell Biol. 2008. 28: 52095222.
  • 24
    Oh-Hora, M., Yamashita, M., Hogan, P. G., Sharma, S., Lamperti, E., Chung, W., Prakriya, M. et al., Dual functions for the endoplasmic reticulum calcium sensors STIM1 and STIM2 in T cell activation and tolerance. Nat. Immunol. 2008. 9: 432443.
  • 25
    Picard, C., McCarl, C. A., Papolos, A., Khalil, S., Luthy, K., Hivroz, C., LeDeist, F. et al., STIM1 mutation associated with a syndrome of immunodeficiency and autoimmunity. N. Engl. J. Med. 2009. 360: 19711980.
  • 26
    Feske, S., Gwack, Y., Prakriya, M., Srikanth, S., Puppel, S.-H., Tanasa, B., Hogan, P. G. et al., A mutation in Orai1 causes immune deficiency by abrogating CRAC channel function. Nature 2006. 441: 179185.
  • 27
    Brandman, O., Liou, J., Park, W. S. and Meyer, T., STIM2 is a feedback regulator that stabilizes basal cytosolic and endoplasmic reticulum Ca2+ levels. Cell 2007. 131: 13271339.
  • 28
    Schuhmann, M. K., Stegner, D., Berna-Erro, A., Bittner, S., Braun, A., Kleinschnitz, C., Stoll, G. et al., Stromal interaction molecules 1 and 2 are key regulators of autoreactive T cell activation in murine autoimmune central nervous system inflammation. J. Immunol. 2010. 184: 15361542.
  • 29
    Brustle, A., Heink, S., Huber, M., Rosenplanter, C., Stadelmann, C., Yu, P., Arpaia, E. et al., The development of inflammatory T(H)-17 cells requires interferon-regulatory factor 4. Nat. Immunol. 2007. 8: 958966.
  • 30
    Hermann-Kleiter, N. and Baier, G., NFAT pulls the strings during CD4+ T helper cell effector functions. Blood 2010. 115: 29892997.
  • 31
    Langrish, C. L., Chen, Y., Blumenschein, W. M., Mattson, J., Basham, B., Sedgwick, J. D., McClanahan, T. et al., IL-23 drives a pathogenic T cell population that induces autoimmune inflammation. J. Exp. Med. 2005. 201: 233240.
  • 32
    Bach, T. L., Chen, Q. M., Kerr, W. T., Wang, Y., Lian, L., Choi, J. K., Wu, D. et al., Phospholipase cbeta is critical for T cell chemotaxis. J. Immunol. 2007. 179: 22232227.
  • 33
    Reboldi, A., Coisne, C., Baumjohann, D., Benvenuto, F., Bottinelli, D., Lira, S., Uccelli, A. et al., C-C chemokine receptor 6-regulated entry of TH-17 cells into the CNS through the choroid plexus is required for the initiation of EAE. Nat. Immunol. 2009. 10: 514523.
  • 34
    Liston, A., Kohler, R. E., Townley, S., Haylock-Jacobs, S., Comerford, I., Caon, A. C., Webster, J. et al., Inhibition of CCR6 function reduces the severity of experimental autoimmune encephalomyelitis via effects on the priming phase of the immune response. J. Immunol. 2009. 182: 31213130.
  • 35
    Yamazaki, T., Yang, X. O., Chung, Y., Fukunaga, A., Nurieva, R., Pappu, B., Martin-Orozco, N. et al., CCR6 regulates the migration of inflammatory and regulatory T cells. J. Immunol. 2008. 181: 83918401.
  • 36
    Beyersdorf, N., Braun, A., Vogtle, T., Varga-Szabo, D., Galdos, R. R., Kissler, S., Kerkau, T. and Nieswandt, B., STIM1-independent T cell development and effector function in vivo. J. Immunol. 2009. 182: 33903397.
  • 37
    Baba, Y., Nishida, K., Fujii, Y., Hirano, T., Hikida, M. and Kurosaki, T., Essential function for the calcium sensor STIM1 in mast cell activation and anaphylactic responses. Nat. Immunol. 2008. 9: 8188.
  • 38
    Macian, F., NFAT proteins: key regulators of T-cell development and function. Nat. Rev. Immunol. 2005. 5: 472484.
  • 39
    Gomez-Rodriguez, J., Sahu, N., Handon, R., Davidson, T. S., Anderson, S. M., Kirby, M. R., August, A. and Schwartzberg, P. L., Differential expression of interleukin-17A and -17F is coupled to T cell receptor signaling via inducible T cell kinase. Immunity 2009. 31: 587597.
  • 40
    Cua, D. J., Sherlock, J., Chen, Y., Murphy, C. A., Joyce, B., Seymour, B., Lucian, L. et al., Interleukin-23 rather than interleukin-12 is the critical cytokine for autoimmune inflammation of the brain. Nature 2003. 421: 744748.
  • 41
    Renno, T., Krakowski, M., Piccirillo, C., Lin, J. Y. and Owens, T., TNF-alpha expression by resident microglia and infiltrating leukocytes in the central nervous system of mice with experimental allergic encephalomyelitis. Regulation by Th1 cytokines. J. Immunol. 1995. 154: 944953.
  • 42
    Merrill, J. E., Kono, D. H., Clayton, J., Ando, D. G., Hinton, D. R. and Hofman, F. M., Inflammatory leukocytes and cytokines in the peptide-induced disease of experimental allergic encephalomyelitis in SJL and B10. PL mice. Proc. Natl. Acad. Sci. USA 1992. 89: 574578.
  • 43
    Kroenke, M. A., Carlson, T. J., Andjelkovic, A. V. and Segal, B. M., 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. 2008. 205: 15351541.
  • 44
    Stromnes, I. M., Cerretti, L. M., Liggitt, D., Harris, R. A. and Goverman, J. M., Differential regulation of central nervous system autoimmunity by T(H)1 and T(H)17 cells. Nat. Med. 2008. 14: 337342.
  • 45
    El-Behi, M., Rostami, A. and Ciric, B., Current Views on the Roles of Th1 and Th17 Cells in Experimental Autoimmune Encephalomyelitis. J. Neuroimmune. Pharmacol. 2010. 5: 189197.
  • 46
    Fife, B. T., Huffnagle, G. B., Kuziel, W. A. and Karpus, W. J., CC chemokine receptor 2 is critical for induction of experimental autoimmune encephalomyelitis. J. Exp. Med. 2000. 192: 899905.
  • 47
    Izikson, L., Klein, R. S., Charo, I. F., Weiner, H. L. and Luster, A. D., Resistance to experimental autoimmune encephalomyelitis in mice lacking the CC chemokine receptor (CCR)2. J. Exp. Med. 2000. 192: 10751080.
  • 48
    Kuwabara, T., Ishikawa, F., Yasuda, T., Aritomi, K., Nakano, H., Tanaka, Y., Okada, Y. et al., CCR7 ligands are required for development of experimental autoimmune encephalomyelitis through generating IL-23-dependent Th17 cells. J. Immunol. 2009. 183: 25132521.
  • 49
    Korn, T., Reddy, J., Gao, W., Bettelli, E., Awasthi, A., Petersen, T. R., Backstrom, B. T. et al., Myelin-specific regulatory T cells accumulate in the CNS but fail to control autoimmune inflammation. Nat. Med. 2007. 13: 423431.
  • 50
    Berna-Erro, A., Braun, A., Kraft, R., Kleinschnitz, C., Schuhmann, M. K., Stegner, D., Wultsch, T. et al., STIM2 regulates capacitive Ca2+ entry in neurons and plays a key role in hypoxic neuronal cell death. Sci. Signal. 2009. 2: ra67.
  • 51
    Abdullaev, I. F., Bisaillon, J. M., Potier, M., Gonzalez, J. C., Motiani, R. K. and Trebak, M., Stim1 and Orai1 mediate CRAC currents and store-operated calcium entry important for endothelial cell proliferation. Circ. Res. 2008. 103: 12891299.
  • 52
    Cioffi, D. L., Barry, C. and Stevens, T., Store-operated calcium entry channels in pulmonary endothelium: the emerging story of TRPCS and Orai1. Adv. Exp. Med. Biol. 2010. 661: 137154.
  • 53
    Ye, J., Tsukamoto, T., Sun, A. and Nigam, S. K., A role for intracellular calcium in tight junction reassembly after ATP depletion-repletion. Am. J. Physiol. 1999. 277: F524532.
  • 54
    Chandy, K. G., Wulff, H., Beeton, C., Pennington, M., Gutman, G. A. and Cahalan, M. D., K+ channels as targets for specific immunomodulation. Trends Pharmacol. Sci. 2004. 25: 280289.
  • 55
    Reich, E. P., Cui, L., Yang, L., Pugliese-Sivo, C., Golovko, A., Petro, M., Vassileva, G. et al., Blocking ion channel KCNN4 alleviates the symptoms of experimental autoimmune encephalomyelitis in mice. Eur. J. Immunol. 2005. 35: 10271036.
  • 56
    Rangaraju, S., Chi, V., Pennington, M. W. and Chandy, K. G., Kv1.3 potassium channels as a therapeutic target in multiple sclerosis. Expert Opin. Ther. Targets 2009. 13: 909924.
  • 57
    Rudge, P., Koetsier, J. C., Mertin, J., Mispelblom Beyer, J. O., Van Walbeek, H. K., Clifford Jones, R., Harrison, J. et al., Randomised double blind controlled trial of cyclosporin in multiple sclerosis. J. Neurol. Neurosurg. Psychiatry 1989. 52: 559565.
  • 58
    Stromnes, I. M. and Goverman, J. M., Active induction of experimental allergic encephalomyelitis. Nat. Protoc. 2006. 1: 18101819.
  • 59
    Collins, M. K., Tay, C. S. and Erlebacher, A., Dendritic cell entrapment within the pregnant uterus inhibits immune surveillance of the maternal/fetal interface in mice. J. Clin. Invest. 2009. 119: 20622073.
  • 60
    Feske, S., Prakriya, M., Rao, A. and Lewis, R. S., A severe defect in CRAC Ca2+ channel activation and altered K+ channel gating in T cells from immunodeficient patients. J. Exp. Med. 2005. 202: 651662.