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Cutting Edge: IL-21 Is Not Essential for Th17 Differentiation or Experimental Autoimmune Encephalomyelitis¹

Jonathan M. Coquet^2,*, Sumone Chakravarti^2,*, Mark J. Smyth^3, and Dale I. Godfrey^3,4,*

^* Department of Microbiology and Immunology, University of Melbourne, Parkville, Victoria, Australia; and Cancer Immunology Program, Peter MacCallum Cancer Centre, St. Andrews Place, East Melbourne, Victoria, Australia

Recent studies have suggested that IL-21 is a key factor in the development of IL-17-producing CD4 T cells (Th17) and that the induction of experimental autoimmune encephalomyelitis, which depends on mounting an efficient Th17 response, is reportedly impaired in the absence of IL-21 signaling. In this study, we provide supportive in vitro evidence that IL-21 can drive Th17 responses in conjunction with TGF-β. However, more importantly we also demonstrate, using IL-21- and IL-21R-deficient mice, that IL-21 is not essential for the differentiation of Th17 cells in vitro and in vivo. Moreover, we show that IL-21- and IL-21R-deficient mice are highly susceptible to experimental autoimmune encephalomyelitis with disease scores that were comparable, or even higher at the peak of disease, to those of control mice. Thus, our results challenge the notion that IL-21 is a key factor in driving Th17 immunity and disease.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This research was funded by National Health and Medical Research Council of Australia (NHMRC) Program Grant 51608 (renewed as Grant 454569). J.M.C. is supported by a Cancer Research Institute postgraduate scholarship. S.C. is supported by an NHMRC Howard Florey Centenary Research Fellowship. D.I.G. and M.J.S. are supported by NHMRC Research Fellowships.

² J.M.C. and S.C. are equal first authors.

³ M.J.S. and D.I.G. are equal chief investigators.

⁴ Address correspondence and reprint requests to Dr. Dale I. Godfrey, Department of Microbiology and Immunology, University of Melbourne, Parkville, 3010 Victoria, Australia. E-mail address: godfrey{at}unimelb.edu.au

⁵ Abbreviations used in this paper: EAE, experimental autoimmune encephalomyelitis; LN, lymph node; MOG, myelin oligodendrocyte glycoprotein; WT, wild type.

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