The cytokine TGF-β co-opts signaling via STAT3-STAT4 to promote the differentiation of human TFH cells.
Nat Immunol 2014 Sep; 15(9):856-65.
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. Nat Immunol 2014 Sep; 15(9):856-65.
Schmitt, Nathalie; Liu, Yang; Bentebibel, Salah-Eddine; Munagala, Indira; Bourdery, Laure; Venuprasad, K; Banchereau, Jacques; and Ueno, Hideki, "The cytokine TGF-β co-opts signaling via STAT3-STAT4 to promote the differentiation of human TFH cells." (2014). Faculty Research 2014. 159.