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

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.