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