Regulation of T Cell Activation and Metabolism by Transforming Growth Factor-Beta

SIMPLE SUMMARY: T cells are a subset of white blood cells that play essential roles in immune protection from a wide range of infectious diseases as well as cancer. By contrast, when immune responses are not controlled properly, T cells can promote damaging inflammation such as that seen in autoimmune diseases. Therefore, the activation of immune responses is tightly regulated in the body with a range of positive and negative signals involved in dictating the nature and extent of T cell responses. Transforming growth factor beta (TGFβ) is a family of proteins, termed cytokines, that have a wide range of roles in the body including an essential role in the regulation of T cell immune responses. Much research effort has gone into understanding the mechanisms by which TGFβ exerts its immune effects with a view to defining new therapies to control T cell responses in autoimmunity and cancer. This review describes recent developments in this research area with a particular focus on effects on T cell metabolism. ABSTRACT: Transforming growth factor beta (TGFβ) receptor signalling regulates T cell development, differentiation and effector function. Expression of the immune-associated isoform of this cytokine, TGFβ1, is absolutely required for the maintenance of immunological tolerance in both mice and humans, whilst context-dependent TGFβ1 signalling regulates the differentiation of both anti- and pro-inflammatory T cell effector populations. Thus, distinct TGFβ-dependent T cell responses are implicated in the suppression or initiation of inflammatory and autoimmune diseases. In cancer settings, TGFβ signals contribute to the blockade of anti-tumour immune responses and disease progression. Given the key functions of TGFβ in the regulation of immune responses and the potential for therapeutic targeting of TGFβ-dependent pathways, the mechanisms underpinning these pleiotropic effects have been the subject of much investigation. This review focuses on accumulating evidence suggesting that modulation of T cell metabolism represents a major mechanism by which TGFβ influences T cell immunity.