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* Neuroimmunology Unit, Department of Neurology, University Hospital Zurich, Zurich, Switzerland;
Ludwig Institute for Cancer Research, Brussels, Belgium;
Christian de Duve Institute of Cellular Pathology, Université Catholique de Louvain, Brussels, Belgium;
Hôpital Pitié Salpetrière, Université Pierre et Marie Curie, Institut National de la Santé et de la Recherche Médicale Unité 543, Paris, France; and
¶ Institute of Neuropathology, University Hospital Zurich, Zurich, Switzerland
Lately, IL-17-secreting Th cells have received an overwhelming amount of attention and are now widely held to be the major pathogenic population in autoimmune diseases. In particular, IL-22-secreting Th17 cells were shown to specifically mark the highly pathogenic population of self-reactive T cells in experimental autoimmune encephalomyelitis (EAE). As IL-17A itself was found to only play a minor role during the development of EAE, IL-22 is now postulated to contribute to the pathogenic function of Th17 cells. The goal of this study was to determine the role and function of IL-22 during the development of CNS autoimmunity in vivo. We found that CNS-invading encephalitogenic Th17 cells coexpress IL-22 and that IL-22 is specifically induced by IL-23 in autoimmune-pathogenic CD4+ T cells in a time- and dose-dependent manner. We next generated IL-22–/– mice, which—in contrast to the prediction that expression of inflammatory cytokines by CNS-invading T cells inevitably confers pathogenic function—turned out to be fully susceptible to EAE. Taken together, we show that self-reactive Th cells coexpress IL-17 and IL-22, but that the latter also does not appear to be directly involved in autoimmune pathogenesis of the CNS.
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1 This work was supported by the Swiss National Science Foundation (to B.B.), the National Center for Competence in Research (to B.B.), the Swiss Multiple Sclerosis Society (to B.B.), Serono Pharmaceuticals Geneva (to B.B.), the Center for Neuroscience Research in Zurich (to K.K.), the Belgian Federal Service for Scientific, Technical, and Cultural Affairs, by the Actions de Recherche Concertées of the Communauté Française de Belgique (to J.-C.R.) and the Fonds National de la Recherche Scientifique, Belgium (to J.-C.R.), and the National Multiple Sclerosis Society (Harry Weaver Neuroscience Scholar; to B.B.).
2 Current address: Medical Research Council Human Immunology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, OX3 9DS, Oxford, U.K.
3 R.E. and L.D. contributed equally to this work.
4 J.-C.R. and B.B. contributed equally to the work.
5 Address correspondence and reprint requests to Dr. Burkhard Becher, Division of Neuroimmunology, Neurology Department, University Hospital, University of Zurich, Winterthurer Strasse 190, CH-8057, Zurich, Switzerland. E-mail address: burkhard.becher{at}neuroimm.unizh.ch
6 Abbreviations used in this paper: MS, multiple sclerosis; EAE, experimental autoimmune encephalomyelitis; MOG, myelin oligodendrocyte glycoprotein; Tg, transgenic; wt, wild type; LN, lymph node; BM, bone marrow; DC, dendritic cell.
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