Literature DB >> 19501566

TGF-beta is necessary for induction of IL-23R and Th17 differentiation by IL-6 and IL-23.

Noriko Morishima1, Izuru Mizoguchi, Kiyoshi Takeda, Junichiro Mizuguchi, Takayuki Yoshimoto.   

Abstract

TGF-beta and IL-6 induce Th17 differentiation, and IL-23 is required for expansion and maintenance of Th17 cells. Recently, it was shown that IL-6 up-regulates IL-23R mRNA in naive CD4+ T cells and therefore IL-6 and IL-23 synergistically promote Th17 differentiation. However, the molecular mechanism whereby IL-6 and IL-23 induce Th17 differentiation and the relevance to TGF-beta remain unknown. Here, we found that IL-6 up-regulated IL-23R mRNA expression, and IL-6 and IL-23 synergistically augmented its protein expression. The combination induced Th17 differentiation, and TGF-beta1 further enhanced it. IL-6 augmented endogenous TGF-beta1 mRNA expression, whereas the amount of TGF-beta produced was not enough to induce Th17 differentiation by IL-6 alone. However, unexpectedly, the up-regulation of IL-23R and induction of Th17 differentiation by IL-6 and IL-23 were almost completely inhibited by anti-TGF-beta. These results suggest that the induction of IL-23R and Th17 differentiation by IL-6 and IL-23 is mediated through endogenously produced TGF-beta.

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Year:  2009        PMID: 19501566     DOI: 10.1016/j.bbrc.2009.05.140

Source DB:  PubMed          Journal:  Biochem Biophys Res Commun        ISSN: 0006-291X            Impact factor:   3.575


  33 in total

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