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The cytokine TGF-? co-opts signaling via STAT3-STAT4 to promote the differentiation of human TFH cells.

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-? (TGF-?) 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 ROR?t, 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.

SUBMITTER: Schmitt N

PROVIDER: S-EPMC4183221 | biostudies-literature | 2014 Sep

REPOSITORIES: biostudies-literature

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The cytokine TGF-β co-opts signaling via STAT3-STAT4 to promote the differentiation of human TFH cells.

Schmitt Nathalie N Liu Yang Y Bentebibel Salah-Eddine SE Munagala Indira I Bourdery Laure L Venuprasad K K Banchereau Jacques J Ueno Hideki H Ueno Hideki H

Nature immunology 20140727 9

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. ...[more]

PMID: 25064073

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