First Author | Morishima N | Year | 2009 |
Journal | Biochem Biophys Res Commun | Volume | 386 |
Issue | 1 | Pages | 105-10 |
PubMed ID | 19501566 | Mgi Jnum | J:150655 |
Mgi Id | MGI:3851279 | Doi | 10.1016/j.bbrc.2009.05.140 |
Citation | Morishima N, et al. (2009) TGF-beta is necessary for induction of IL-23R and Th17 differentiation by IL-6 and IL-23. Biochem Biophys Res Commun 386(1):105-10 |
abstractText | 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. |