The cytokine TGF-β 2 co-opts signaling via STAT3-STAT4 to promote the differentiation of human T FH cells

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

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140 Scopus citations

Abstract

Understanding the developmental mechanisms of follicular helper T cells (T FH cells) in humans is relevant to the clinic. However, the factors that drive the differentiation of human CD4 + helper T cells into T FH cells remain largely undefined. Here we found that transforming growth factor-β 2 (TGF-β 2) provided critical additional signals for the transcription factors STAT3 and STAT4 to promote initial T FH differentiation in humans. This mechanism did not appear to be shared by mouse helper T cells. Developing human T FH cells that expressed the transcriptional repressor Bcl-6 also expressed RORγ 3t, a transcription factor typically expressed by the T H 17 subset of helper T cells. Our study documents a mechanism by which T FH cells and T H 17 cells emerge together in inflammatory environments in humans, as is often observed in many human autoimmune diseases.

Original languageEnglish (US)
Pages (from-to)856-865
Number of pages10
JournalNature Immunology
Volume15
Issue number9
DOIs
StatePublished - Sep 2014

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ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Schmitt, N., Liu, Y., Bentebibel, S. E., Munagala, I., Bourdery, L., Venuprasad, K., Banchereau, J., & Ueno, H. (2014). The cytokine TGF-β 2 co-opts signaling via STAT3-STAT4 to promote the differentiation of human T FH cells. Nature Immunology, 15(9), 856-865. https://doi.org/10.1038/ni.2947