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The Cytokine TGF-β Co-Opts Signaling via STAT3-STAT4 to Promote the Differentiation of Human TFH Cells

The Cytokine TGF-β Co-Opts Signaling via STAT3-STAT4 to Promote the Differentiation of Human TFH Cells

Nathalie Schmitt, Yang Liu, Salah-Eddine Bentebibel, Indira Munagala, Laure Bourdery, K Venuprasad, Jacques Banchereau, Hideki Ueno

Nat Immunol. 2014 Sep;15(9):856-65.

PMID: 25064073

Abstract:

Understanding the developmental mechanisms of follicular helper T cells (TFH cells) in humans is relevant to the clinic. However, the factors that drive the differentiation of human CD4+ helper T cells into TFH cells remain largely undefined. Here we found that transforming growth factor-β (TGF-β) provided critical additional signals for the transcription factors STAT3 and STAT4 to promote initial TFH differentiation in humans. This mechanism did not appear to be shared by mouse helper T cells. Developing human TFH cells that expressed the transcriptional repressor Bcl-6 also expressed RORγt, a transcription factor typically expressed by the TH17 subset of helper T cells. Our study documents a mechanism by which TFH cells and TH17 cells emerge together in inflammatory environments in humans, as is often observed in many human autoimmune diseases.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
IAR42415001	STAT4 human			Price

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