Controlling Immunity and Inflammation through Integrin-Dependent Regulation of TGF-β

Integrins promote cell adhesion and migration, but also control local activation of latent transforming growth factor (TGF)-beta contained in extracellular matrix or cell-surface reservoirs. Integrin-dependent activation of TGF-beta has emerged as a crucial mechanism whereby tissue-borne cells instruct circulating and resident immune cells. Moreover, this regulation has wide patho-physiological implications in wound healing, tissue fibrosis, antibody production, pathogen clearance, inflammation, autoimmunity, cancer, and possibly metabolic disorders including diabetes. Here we review the spatiotemporal control of TGF-beta activation by integrins, and its effects on immune cell signaling and function. We discuss the underlying molecular and cell-biological mechanisms, the implications for human health and disease, and possibilities for future therapeutic exploitation.