Transforming growth factor–β1 in regulatory T cell biology

Transforming growth factor-β1 (TGF-β1) is inextricably linked to regulatory T cell (Treg) biology. However, precisely untangling the role for TGF-β1 in Treg differentiation and function is complicated by the pleiotropic and context-dependent activity of this cytokine and the multifaceted biology of Tregs. Among CD4+ T cells, Tregs are the major producers of latent TGF-β1 and are uniquely able to activate this cytokine via expression of cell surface docking receptor glycoprotein A repetitions predominant (GARP) and αv integrins. Although a preponderance of evidence indicates no essential roles for Treg-derived TGF-β1 in Treg immunosuppression, TGF-β1 signaling is crucial for Treg development in the thymus and periphery. Furthermore, active TGF-β1 instructs the differentiation of other T cell subsets, including TH17 cells. Here, we will review TGF-β1 signaling in Treg development and function and discuss knowledge gaps, future research, and the TGF-β1/Treg axis in the context of cancer immunotherapy and fibrosis.