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

Research output: Contribution to journalArticle

135 Citations (Scopus)

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
Externally publishedYes

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Transforming Growth Factors
Cytokines
Helper-Inducer T-Lymphocytes
STAT4 Transcription Factor
Th17 Cells
STAT3 Transcription Factor
Autoimmune Diseases
Transcription Factors

ASJC Scopus subject areas

  • Immunology

Cite this

The cytokine TGF-β 2 co-opts signaling via STAT3-STAT4 to promote the differentiation of human T FH cells. / Schmitt, Nathalie; Liu, Yang; Bentebibel, Salah Eddine; Munagala, Indira; Bourdery, Laure; Venuprasad, K.; Banchereau, Jacques; Ueno, Hideki.

In: Nature Immunology, Vol. 15, No. 9, 09.2014, p. 856-865.

Research output: Contribution to journalArticle

Schmitt, N, Liu, Y, Bentebibel, SE, 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, vol. 15, no. 9, pp. 856-865. https://doi.org/10.1038/ni.2947
Schmitt, Nathalie ; Liu, Yang ; Bentebibel, Salah Eddine ; Munagala, Indira ; Bourdery, Laure ; Venuprasad, K. ; Banchereau, Jacques ; Ueno, Hideki. / The cytokine TGF-β 2 co-opts signaling via STAT3-STAT4 to promote the differentiation of human T FH cells. In: Nature Immunology. 2014 ; Vol. 15, No. 9. pp. 856-865.
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