IL‐21 and IL‐21R are not required for development of Th17 cells and autoimmunity in vivo

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Abstract
Th17 cells have been recognized as the central effectors in organ-related autoimmune diseases. IL-6 is a key factor that reciprocally regulates Th17 and Foxp3+ Treg differentiation by inhibition of TGF-β induced Foxp3 and induction of RORγt, a Th17 lineage-specific transcription factor. Recently IL-21 has been suggested to induce RORγt and Th17 development in the absence of IL-6. However, the relevance of IL-21 for Th17-dependent inflammatory responses in vivo remains unclear. In this study, we demonstrate that differentiation of IL-17-producing CD4 T cells, their recruitment to inflamed organs, and the development of autoimmune disease was not affected in il21R–/– and il21–/– mice in models of myelin oligodendrocyte glycoprotein-induced autoimmune encephalitis and autoimmune myocarditis. IL-6 induced Th17 differentiation independent of and much more potently than IL-21 in vitro. These data suggest that IL-6 is sufficient to drive Th17 development and associated autoimmunity in vivo in the absence of IL-21 or IL-21R. See accompanying Commentary http:dx.doi.org/10.1002/eji.200838529 Supporting information for this article is available at http://www.wiley-vch.de/contents/jc_2040/2008/38511_s.pdf