TGFβ in the context of an inflammatory cytokine milieu supports de novo differentiation of IL-17-producing T cells

被引：3310

作者：

Veldhoen, M

Hocking, RJ

Atkins, CJ

Locksley, RM

Stockinger, B

机构：

[1] Natl Inst Med Res, MRC, Div Mol Immunol, London NW7 1AA, England

[2] Univ Calif San Francisco, Natl Inst Med Res, Div Immunoregulat, San Francisco, CA 94143 USA

[3] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA

[4] Univ Calif San Francisco, Dept Microbiol Immunol, San Francisco, CA 94143 USA

来源：

IMMUNITY | 2006年 / 24卷 / 02期

关键词：

D O I：

10.1016/j.immuni.2006.01.001

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

We describe de novo generation of IL-17-producing T cells from naive CD4 T cells, induced in cocultures of naive CD4 T cells and naturally occurring CD4(+) CD25(+) T cells (Treg) in the presence of TLR3, TLR4, or TLR9 stimuli. Treg can be substituted by TGF beta 1, which, together with the proinflammatory cytokine IL-6, supports the differentiation of IL-17-producing T cells, a process that is amplified by IL-1 beta and TNF alpha. We could not detect a role for IL-23 in the differentiation of IL-17-producing T cells but confirmed its importance for their survival and expansion. Transcription factors GATA-3 and T-bet, as well as its target Hlx, are absent in IL-17-producing T cells, and they do not express the negative regulator for TGF beta signaling, Smad7. Our data indicate that, in the presence of IL-6, TGF beta 1 subverts Th1 and Th2 differentiation for the generation of IL-17-producing T cells.

引用

页码：179 / 189

页数：11

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