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

Abstract：

: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 TGFbeta1, which, together with the proinflammatory cytokine IL-6, supports the differentiation of IL-17-producing T cells, a process that is amplified by IL-1beta and TNFalpha. 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 TGFbeta signaling, Smad7. Our data indicate that, in the presence of IL-6, TGFbeta1 subverts Th1 and Th2 differentiation for the generation of IL-17-producing T cells.

journal_name

Immunity

journal_title

Immunity

authors

Veldhoen M,Hocking RJ,Atkins CJ,Locksley RM,Stockinger B

doi

10.1016/j.immuni.2006.01.001

keywords:

subject

Has Abstract

pub_date

2006-02-01 00:00:00

pages

179-89

issue

2

eissn

1074-7613

issn

1097-4180

pii

S1074-7613(06)00004-5

journal_volume

24

pub_type

杂志文章

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