共 72 条
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
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机构: Natl Inst Med Res, MRC, Div Mol Immunol, London NW7 1AA, England

Hocking, RJ
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机构: Natl Inst Med Res, MRC, Div Mol Immunol, London NW7 1AA, England

Atkins, CJ
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机构: Natl Inst Med Res, MRC, Div Mol Immunol, London NW7 1AA, England

Locksley, RM
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机构: Natl Inst Med Res, MRC, Div Mol Immunol, London NW7 1AA, England

Stockinger, B
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机构: Natl Inst Med Res, MRC, Div Mol Immunol, London NW7 1AA, England
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
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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.
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页码:179 / 189
页数:11
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