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

被引：92

作者：

Morishima, Noriko ^{[1
,2
]}

Mizoguchi, Izuru ^{[1
,2
]}

Takeda, Kiyoshi ^{[3
]}

Mizuguchi, Junichiro ^{[1
,2
]}

Yoshimoto, Takayuki ^{[1
]}

机构：

[1] Tokyo Med Univ, Intractable Dis Res Ctr, Shinjuku Ku, Tokyo 1608402, Japan

[2] Tokyo Med Univ, Dept Immunol, Shinjuku Ku, Tokyo 1608402, Japan

[3] Osaka Univ, Lab Immune Regulat, Grad Sch Med, Suita, Osaka 5650871, Japan

来源：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 2009年 / 386卷 / 01期

关键词：

IL-6; IL-23; IL-23R; Th17; TGF-beta; T-HELPER-CELLS; TRANSFORMING GROWTH-FACTOR-BETA-1; DESIGNER CYTOKINE; DISTINCT; LINEAGE; INTERLEUKIN-17; INFLAMMATION; TOLERANCE; STAT3; SOCS3;

D O I：

10.1016/j.bbrc.2009.05.140

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

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-beta 1 further enhanced it. IL-6 augmented endogenous TGF-beta 1 mRNA expression, whereas the amount of TGF-beta produced was not enough to induce Th-17 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. (C) 2009 Elsevier Inc. All rights reserved.

引用

页码：105 / 110

页数：6

共 26 条

[1]

T-bet is a STAT1-induced regulator of IL-12R expression in naive CD4+ T cells [J].