Regulation of barrier immunity and homeostasis by integrin-mediated transforming growth factor β activation

Transforming growth factor β (TGF-β) is a multifunctional cytokine that regulates cell growth, differentiation, adhesion, migration and death dependent on cell type, developmental stage, or tissue conditions. Various cell types secrete TGF-β, but always as an inactive complex. Hence, for TGF-β to function, this latent complex must somehow be activated. Work in recent years has highlighted a critical role for members of the α_v integrin family, including α_v β₁ , α_v β₃ , α_v β₅ , α_v β₆ and α_v β₈ that are involved in TGF-β activation in various contexts, particularly at barrier sites such as the gut, lung and skin. The integrins facilitating this context- and location-specific regulation can be dysregulated in certain diseases, so are potential therapeutic targets in a number of disorders. In this review, we discuss the role of TGF-β at these barrier sites with a focus on how integrin-mediated TGF-β activation regulates tissue and immune homeostasis, and how this is altered in disease.