Alpha (v) integrins license regulatory T cells to apoptotic cells and self-associated antigens

Defects in apoptotic cell clearance are thought to contribute to autoimmunity by failure to induce tolerance, coupled with accumulation of immunogenic material. However, little is known about the contribution of apoptosis to immune responses at mucosal sites, where regulatory T cells (T-reg cells) and other immune cells play an essential active role in maintaining tolerance to self-associated antigens. In recent studies, we have found that alpha(v) integrins have an important role in apoptotic cell phagocytosis and induction of T-reg cells in the intestine, and deletion of alpha(v) from myeloid cells causes colitis associated with failed apoptotic cell removal and loss of T-reg cells. Our data show that activation of transforming growth factor (TGF)-beta by alpha(v)beta(8) on dendritic cells (DCs) is essential for generating Treg cells and inducing mucosa! tolerance. These results provide a mechanism by which tolerance to apoptotic cell derived and associated antigens is maintained by DC licensing at sites of high TGF-beta expression.