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Alpha (v) integrins license regulatory T cells to apoptotic cells and self‐associated antigens
Author(s) -
Païdassi Helena,
Acharya Mridu,
LacyHulbert Adam
Publication year - 2010
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/j.1749-6632.2010.05783.x
Subject(s) - microbiology and biotechnology , cytotoxic t cell , immune system , biology , apoptosis , immune tolerance , antigen , antigen presenting cell , integrin , t cell , immunology , chemistry , cell , biochemistry , genetics , in vitro
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 α v integrins have an important role in apoptotic cell phagocytosis and induction of T reg cells in the intestine, and deletion of α 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)‐β by α v β 8 on dendritic cells (DCs) is essential for generating T reg cells and inducing mucosal 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‐β expression.