The cytokine TGF-β 2 co-opts signaling via STAT3-STAT4 to promote the differentiation of human T _FH cells

Understanding the developmental mechanisms of follicular helper T cells (T _FH cells) in humans is relevant to the clinic. However, the factors that drive the differentiation of human CD4 + helper T cells into T _FH cells remain largely undefined. Here we found that transforming growth factor-β 2 (TGF-β 2) provided critical additional signals for the transcription factors STAT3 and STAT4 to promote initial T _FH differentiation in humans. This mechanism did not appear to be shared by mouse helper T cells. Developing human T _FH cells that expressed the transcriptional repressor Bcl-6 also expressed RORγ 3t, a transcription factor typically expressed by the T _H 17 subset of helper T cells. Our study documents a mechanism by which T _FH cells and T H 17 cells emerge together in inflammatory environments in humans, as is often observed in many human autoimmune diseases.