Tumor Suppressor Functions of TGFβ1 in T Cells

Abstract

Transforming growth factor ~1 (TGF~1) is an important pleiotropic immunoregulatory cytokine, which is involved in several cellular processes, such as inhibition of T-cell activation, proliferation, differentiation, apoptosis, cytokine production, and effector function. In contrast to its inhibitory effects on naive T cells, it is also involved in stimulation of suppressor/regulatory T-cell expansion and function. In order to achieve so many diverse effects TGF~ utilizes distinct signaling mechanisms in the same cell type. Mouse models with genetic ablation of functional TGF~ signaling mediators have revealed several interesting mechanisms that play an important role in T-cell homeostasis, Treg-cell function, and tumorigenesis. TGF~l primarily functions to prevent abnormal T-cell activation through modulation of a Ca2+-calcineurin signaling pathway in a SMAD3/4-independent manner. Additionally, in Trc(J cells TGF~l mediates its effects through a SMAD signaling cascade in a unique manner. TGF~1 plays duel roles in tumor development and progression.