IL-21 and IL-21R are not required for development of Th17 cells and autoimmunity in vivo
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-beta induced Foxp3 and induction of RORgammat, a Th17 lineage-specific transcription factor. Recently IL-21 has been suggested to induce RORgammat 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.
|Authors||Sonderegger, I.; Kisielow, J.; Meier, R.; King, C.; Kopf, M.|
|Publisher Name||EUROPEAN JOURNAL OF IMMUNOLOGY|
|URL link to publisher's version||http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=18546146|
|OpenAccess link to author's accepted manuscript version||https://publications.gimr.garvan.org.au/open-access/10058|