TGF‐β1 signaling and Smad7 control T‐cell responses in health and immune‐mediated disorders

Abstract

AbstractTransforming growth factor (TGF)‐β1, a member of the TGF‐β superfamily, is produced by many immune and nonimmune cells and has pleiotropic effects on both innate and adaptive immunity, especially in the control of T‐cell differentiation and function. Consistently, loss of TGF‐β1 function is associated with exacerbated T‐cell‐dependent inflammatory responses that culminate in pathological processes in allergic and immune‐mediated diseases. In this review, we highlight the roles of TGF‐β1 in immunity, focusing mainly on its ability to promote differentiation of regulatory T cells, T helper (Th)‐17, and Th9 cells, thus contributing to amplifying or restricting T‐cell responses in health and human diseases (e.g., inflammatory bowel diseases, type 1 diabetes, asthma, and MS). In addition, we discuss the involvement of Smad7, an inhibitor of TGF‐β1 signaling, in immune‐mediated disorders (e.g., psoriasis, rheumatoid arthritis, MS, and inflammatory bowel diseases), as well as the discordant results of clinical trials with mongersen, an oral pharmaceutical compound containing a Smad7 antisense oligonucleotide, in patients with Crohn's disease. Further work is needed to ascertain the reasons for such a discrepancy as well as to identify better candidates for treatment with Smad7 inhibitors.