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.
authors.affiliation: Baylor Institute for Immunology Research, Baylor Research Institute, Dallas, TX 75204, USA.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Schmitt
authors.affiliation: Baylor Institute for Immunology Research, Baylor Research Institute, Dallas, TX 75204, USA.
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Baylor Institute for Immunology Research, Baylor Research Institute, Dallas, TX 75204, USA.
authors.forename: Salah-Eddine
authors.initials: SE
authors.lastname: Bentebibel
authors.affiliation: Baylor Institute for Immunology Research, Baylor Research Institute, Dallas, TX 75204, USA. Electronic address: hideki.ueno@mssm.edu.
authors.forename: Hideki
authors.initials: H
authors.lastname: Ueno
mesh_terms: D001402:B-Lymphocytes / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002454:Cell Differentiation / Q000276:immunology*; D002478:Cells, Cultured; D006801:Humans; D050835:Interferon Regulatory Factors / Q000276:immunology; D018664:Interleukin-12 / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D054380:Receptors, CXCR5 / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D014157:Transcription Factors / Q000276:immunology; D000099218:Interferon Regulatory Factor-4
chemical_list: D050835:Interferon Regulatory Factors; D018664:Interleukin-12; D054380:Receptors, CXCR5; D014157:Transcription Factors; D000099218:Interferon Regulatory Factor-4