TGF-β co-opts STAT3-STAT4 signaling to promote human T follicular helper cell differentiation

Understanding the developmental mechanisms of T follicular helper (T(FH)) cells in humans is a highly relevant topic to clinic. However, factors that drive human CD4(+) helper T (T(H)) cell differentiation program towards T(FH) cells remain largely undefined. Here we show that TGF-β provides critica...

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Autores principales: Schmitt, Nathalie, Liu, Yang, Bentebibel, Salah-Eddine, Munagala, Indira, Bourdery, Laure, Venuprasad, K, Banchereau, Jacques, Ueno, Hideki
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2014
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4183221/
https://www.ncbi.nlm.nih.gov/pubmed/25064073
http://dx.doi.org/10.1038/ni.2947
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author Schmitt, Nathalie
Liu, Yang
Bentebibel, Salah-Eddine
Munagala, Indira
Bourdery, Laure
Venuprasad, K
Banchereau, Jacques
Ueno, Hideki
author_facet Schmitt, Nathalie
Liu, Yang
Bentebibel, Salah-Eddine
Munagala, Indira
Bourdery, Laure
Venuprasad, K
Banchereau, Jacques
Ueno, Hideki
author_sort Schmitt, Nathalie
collection PubMed
description Understanding the developmental mechanisms of T follicular helper (T(FH)) cells in humans is a highly relevant topic to clinic. However, factors that drive human CD4(+) helper T (T(H)) cell differentiation program towards T(FH) cells remain largely undefined. Here we show that TGF-β provides critical additional signals for the transcription factors STAT3 and STAT4 to promote the initial T(FH) differentiation programs in humans. This mechanism does not appear to be shared with mouse T(H) cells. The developing human Bcl-6(+) T(FH) cells also expressed RORγt, a transcription factor typically expressed by T(H)17 cells. Our study documents a mechanism by which T(FH) and T(H)17 cells co-emerge in inflammatory environments in humans, as often observed in many human autoimmune diseases.
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spelling pubmed-41832212015-03-01 TGF-β co-opts STAT3-STAT4 signaling to promote human T follicular helper cell differentiation Schmitt, Nathalie Liu, Yang Bentebibel, Salah-Eddine Munagala, Indira Bourdery, Laure Venuprasad, K Banchereau, Jacques Ueno, Hideki Nat Immunol Article Understanding the developmental mechanisms of T follicular helper (T(FH)) cells in humans is a highly relevant topic to clinic. However, factors that drive human CD4(+) helper T (T(H)) cell differentiation program towards T(FH) cells remain largely undefined. Here we show that TGF-β provides critical additional signals for the transcription factors STAT3 and STAT4 to promote the initial T(FH) differentiation programs in humans. This mechanism does not appear to be shared with mouse T(H) cells. The developing human Bcl-6(+) T(FH) cells also expressed RORγt, a transcription factor typically expressed by T(H)17 cells. Our study documents a mechanism by which T(FH) and T(H)17 cells co-emerge in inflammatory environments in humans, as often observed in many human autoimmune diseases. 2014-07-27 2014-09 /pmc/articles/PMC4183221/ /pubmed/25064073 http://dx.doi.org/10.1038/ni.2947 Text en http://www.nature.com/authors/editorial_policies/license.html#terms Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms
spellingShingle Article
Schmitt, Nathalie
Liu, Yang
Bentebibel, Salah-Eddine
Munagala, Indira
Bourdery, Laure
Venuprasad, K
Banchereau, Jacques
Ueno, Hideki
TGF-β co-opts STAT3-STAT4 signaling to promote human T follicular helper cell differentiation
title TGF-β co-opts STAT3-STAT4 signaling to promote human T follicular helper cell differentiation
title_full TGF-β co-opts STAT3-STAT4 signaling to promote human T follicular helper cell differentiation
title_fullStr TGF-β co-opts STAT3-STAT4 signaling to promote human T follicular helper cell differentiation
title_full_unstemmed TGF-β co-opts STAT3-STAT4 signaling to promote human T follicular helper cell differentiation
title_short TGF-β co-opts STAT3-STAT4 signaling to promote human T follicular helper cell differentiation
title_sort tgf-β co-opts stat3-stat4 signaling to promote human t follicular helper cell differentiation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4183221/
https://www.ncbi.nlm.nih.gov/pubmed/25064073
http://dx.doi.org/10.1038/ni.2947
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