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TGF-β induces the expression of the adaptor Ndfip1 to silence IL-4 production during iTreg cell differentiation.

Abstract：

:Mice deficient in the adaptor Ndfip1 develop inflammation at sites of environmental antigen exposure. We show here that such mice had fewer inducible regulatory T cells (iT(reg) cells). In vitro, Ndfip1-deficient T cells expressed normal amounts of the transcription factor Foxp3 during the first 48 h of iT(reg) cell differentiation; however, this expression was not sustained. Abortive Foxp3 expression was caused by production of interleukin 4 (IL-4) by Ndfip1(-/-) cells. We found that Ndfip1 expression was transiently upregulated during iT(reg) cell differentiation in a manner dependent on transforming growth factor-β (TGF-β). Once expressed, Ndfip1 promoted degradation of the transcription factor JunB mediated by the E3 ubiquitin ligase Itch, thus preventing IL-4 production. On the basis of our data, we propose that TGF-β signaling induces Ndfip1 expression to silence IL-4 production, thus permitting iT(reg) cell differentiation.

journal_name

Nat Immunol

journal_title

Nature immunology

authors

Beal AM,Ramos-Hernández N,Riling CR,Nowelsky EA,Oliver PM

doi

10.1038/ni.2154

subject

Has Abstract

pub_date

2011-11-13 00:00:00

pages

77-85

issue

1

eissn

1529-2908

issn

1529-2916

pii

ni.2154

journal_volume

13

pub_type

杂志文章

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