Aryl hydrocarbon receptor regulates Stat1 activation and participates in the development of Th17 cells

被引：423

作者：

Kimura, Akihiro ^{[1
]}

Naka, Tetsuji ^{[2
]}

Nohara, Keiko ^{[3
]}

Fujii-Kuriyama, Yoshiaki ^{[4
,5
]}

Kishimoto, Tadamitsu ^{[1
]}

机构：

[1] Osaka Univ, Grad Sch Frontier Biosci, Lab Immune Regulat, Suita, Osaka 5650871, Japan

[2] Natl Inst Biomed Innovat, Lab Immune Signal, Osaka 5670085, Japan

[3] Natl Inst Environm Studies, Environm Hlth Sci Div, Tsukuba, Ibaraki 3058506, Japan

[4] Univ Tsukuba, Ctr Tsukuba Adv Res Alliance, Tsukuba, Ibaraki 3058577, Japan

[5] Univ Tsukuba, Inst Basic Med Sci, Tsukuba, Ibaraki 3058577, Japan

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2008年 / 105卷 / 28期

关键词：

dioxin receptor; IL-17; IL-6; ROR; regulatory T cells;

D O I：

10.1073/pnas.0804231105

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

IL-17-producing T helper cells (Th17) have been recently identified as a previously undescribed subset of helper T cells. Here, we demonstrate that aryl hydrocarbon receptor (Ahr) has an important regulatory function in the commitment of Th17 cells. Ahr was robustly induced under Th17-polarizing conditions. Ahr-deficient naive T cells showed a considerable loss in the ability to differentiate into Th17 cells when induced by TGF-beta plus IL-6. We were able to demonstrate that Ahr interacts with Stat1 and Stat5, which negatively regulate Th17 development. Whereas Stat1 activation returned to its basal level in Ahr wild type naive T cells 24 h after stimulation with TGF-beta plus IL-6, Stat1 remained activated in Ahr-deficient naive T cells after stimulation. These results indicate that Ahr participates in Th17 cell differentiation through regulating Stat1 activation, a finding that constitutes additional mechanisms in the modulation of Th17 cell development.

引用

页码：9721 / 9726

页数：6

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