Stromal cells control the epithelial residence of DCs and memory T cells by regulated activation of TGF-β

Cells of the immune system that reside in barrier epithelia provide a first line of defense against pathogens. Langerhans cells (LCs) and CD8 + tissue-resident memory T cells (T RM cells) require active transforming growth factor-β1 (TGF-β) for epidermal residence. Here we found that integrins α v β 6 and α v β 8 were expressed in non-overlapping patterns by keratinocytes (KCs) and maintained the epidermal residence of LCs and T RM cells by activating latent TGF-β. Similarly, the residence of dendritic cells and T RM cells in the small intestine epithelium also required α v β 6. Treatment of the skin with ultraviolet irradiation decreased integrin expression on KCs and reduced the availability of active TGF-β, which resulted in LC migration. Our data demonstrated that regulated activation of TGF-β by stromal cells was able to directly control epithelial residence of cells of the immune system through a novel mechanism of intercellular communication.