title: The cytokine TGF-β co-opts signaling via STAT3-STAT4 to promote the differentiation of human TFH cells.
abstract: Understanding the developmental mechanisms of follicular helper T cells (TFH cells) in humans is relevant to the clinic. However, the factors that drive the differentiation of human CD4+ helper T cells into TFH cells remain largely undefined. Here we found that transforming growth factor-β (TGF-β) provided critical additional signals for the transcription factors STAT3 and STAT4 to promote initial TFH differentiation in humans. This mechanism did not appear to be shared by mouse helper T cells. Developing human TFH cells that expressed the transcriptional repressor Bcl-6 also expressed RORγt, a transcription factor typically expressed by the TH17 subset of helper T cells. Our study documents a mechanism by which TFH cells and TH17 cells emerge together in inflammatory environments in humans, as is often observed in many human autoimmune diseases.
authors: Baylor Institute for Immunology Research, Baylor Research Institute, Dallas, Texas, USA.
authors: Nathalie
authors: N
authors: Schmitt
authors: Baylor Institute for Immunology Research, Baylor Research Institute, Dallas, Texas, USA.
authors: Yang
authors: Y
authors: Liu
authors: Baylor Institute for Immunology Research, Baylor Research Institute, Dallas, Texas, USA.
authors: Salah-Eddine
authors: SE
authors: Bentebibel
authors: Baylor Institute for Immunology Research, Baylor Research Institute, Dallas, Texas, USA.
authors: Indira
authors: I
authors: Munagala
authors: Baylor Institute for Immunology Research, Baylor Research Institute, Dallas, Texas, USA.
authors: Laure
authors: L
authors: Bourdery
authors: Baylor Institute for Immunology Research, Baylor Research Institute, Dallas, Texas, USA.
authors: K
authors: K
authors: Venuprasad
authors: 1] Baylor Institute for Immunology Research, Baylor Research Institute, Dallas, Texas, USA. [2].
authors: Jacques
authors: J
authors: Banchereau
authors: Baylor Institute for Immunology Research, Baylor Research Institute, Dallas, Texas, USA.
authors: Hideki
authors: 0000000271283816
authors: H
authors: Ueno
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000276:immunology*; D004268:DNA-Binding Proteins / Q000276:immunology; D018858:Germinal Center / Q000276:immunology*; D006801:Humans; D051379:Mice; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3 / Q000276:immunology; D051560:Proto-Oncogene Proteins c-bcl-6; D050796:STAT3 Transcription Factor / Q000276:immunology*; D050797:STAT4 Transcription Factor / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D058504:Th17 Cells / Q000276:immunology*; D016212:Transforming Growth Factor beta
chemical_list: C084103:BCL6 protein, human; D004268:DNA-Binding Proteins; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; D051560:Proto-Oncogene Proteins c-bcl-6; C539900:RORC protein, human; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D050797:STAT4 Transcription Factor; C494090:STAT4 protein, human; C494087:Stat3 protein, mouse; C494091:Stat4 protein, mouse; D016212:Transforming Growth Factor beta