Molecular Mechanisms Regulating T Helper 1 versus T Follicular Helper Cell Differentiation in Humans

Nathalie Schmitt; Yang Liu; Salah Eddine Bentebibel; Hideki Ueno

doi:10.1016/j.celrep.2016.06.063

Molecular Mechanisms Regulating T Helper 1 versus T Follicular Helper Cell Differentiation in Humans

Nathalie Schmitt
, Yang Liu
, Salah Eddine Bentebibel
, Hideki Ueno

Research output: Contribution to journal › Article › peer-review

42 Scopus citations

Abstract

IL-12 is important for the differentiation of T follicular helper (Tfh) cells, as well as Th1 cells in humans. Still, how IL-12 signals regulate Tfh versus Th1 cell differentiation remains poorly characterized. Here we aimed to determine the molecular mechanisms that regulate the differentiation and the function of IL-12-stimulated human naive CD4⁺ T cells. We found that T-bet promoted the expression of CXCR5 in human CD4⁺ T cells. We provide evidence that T-bet does not strongly inhibit the Tfh cell differentiation program per se but diminishes the functions to provide help to B cells. This study also suggests that IRF4 plays an important role in driving the early differentiation of IL-12-stimulated CD4⁺ T cells toward Tfh and away from Th1 by inhibiting the expression of Eomesodermin. Thus, the fate of IL-12-stimulated CD4⁺ T cells is determined through interplay of multiple transcription factors at early stages.

Original language	English
Pages (from-to)	1082-1095
Number of pages	14
Journal	Cell Reports
Volume	16
Issue number	4
DOIs	https://doi.org/10.1016/j.celrep.2016.06.063
State	Published - 26 Jul 2016
Externally published	Yes

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title = "Molecular Mechanisms Regulating T Helper 1 versus T Follicular Helper Cell Differentiation in Humans",

abstract = "IL-12 is important for the differentiation of T follicular helper (Tfh) cells, as well as Th1 cells in humans. Still, how IL-12 signals regulate Tfh versus Th1 cell differentiation remains poorly characterized. Here we aimed to determine the molecular mechanisms that regulate the differentiation and the function of IL-12-stimulated human naive CD4+ T cells. We found that T-bet promoted the expression of CXCR5 in human CD4+ T cells. We provide evidence that T-bet does not strongly inhibit the Tfh cell differentiation program per se but diminishes the functions to provide help to B cells. This study also suggests that IRF4 plays an important role in driving the early differentiation of IL-12-stimulated CD4+ T cells toward Tfh and away from Th1 by inhibiting the expression of Eomesodermin. Thus, the fate of IL-12-stimulated CD4+ T cells is determined through interplay of multiple transcription factors at early stages.",

author = "Nathalie Schmitt and Yang Liu and Bentebibel, \{Salah Eddine\} and Hideki Ueno",

note = "Publisher Copyright: {\textcopyright} 2016 The Authors",

year = "2016",

month = jul,

day = "26",

doi = "10.1016/j.celrep.2016.06.063",

language = "English",

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T1 - Molecular Mechanisms Regulating T Helper 1 versus T Follicular Helper Cell Differentiation in Humans

AU - Schmitt, Nathalie

AU - Liu, Yang

AU - Bentebibel, Salah Eddine

AU - Ueno, Hideki

PY - 2016/7/26

Y1 - 2016/7/26

N2 - IL-12 is important for the differentiation of T follicular helper (Tfh) cells, as well as Th1 cells in humans. Still, how IL-12 signals regulate Tfh versus Th1 cell differentiation remains poorly characterized. Here we aimed to determine the molecular mechanisms that regulate the differentiation and the function of IL-12-stimulated human naive CD4+ T cells. We found that T-bet promoted the expression of CXCR5 in human CD4+ T cells. We provide evidence that T-bet does not strongly inhibit the Tfh cell differentiation program per se but diminishes the functions to provide help to B cells. This study also suggests that IRF4 plays an important role in driving the early differentiation of IL-12-stimulated CD4+ T cells toward Tfh and away from Th1 by inhibiting the expression of Eomesodermin. Thus, the fate of IL-12-stimulated CD4+ T cells is determined through interplay of multiple transcription factors at early stages.

AB - IL-12 is important for the differentiation of T follicular helper (Tfh) cells, as well as Th1 cells in humans. Still, how IL-12 signals regulate Tfh versus Th1 cell differentiation remains poorly characterized. Here we aimed to determine the molecular mechanisms that regulate the differentiation and the function of IL-12-stimulated human naive CD4+ T cells. We found that T-bet promoted the expression of CXCR5 in human CD4+ T cells. We provide evidence that T-bet does not strongly inhibit the Tfh cell differentiation program per se but diminishes the functions to provide help to B cells. This study also suggests that IRF4 plays an important role in driving the early differentiation of IL-12-stimulated CD4+ T cells toward Tfh and away from Th1 by inhibiting the expression of Eomesodermin. Thus, the fate of IL-12-stimulated CD4+ T cells is determined through interplay of multiple transcription factors at early stages.

UR - https://www.scopus.com/pages/publications/84978864135

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JO - Cell Reports

JF - Cell Reports

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ER -

Molecular Mechanisms Regulating T Helper 1 versus T Follicular Helper Cell Differentiation in Humans

Abstract

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