title: Role of the glucocorticoid-induced TNFR-related protein (GITR)-GITR ligand pathway in innate and adaptive immunity.
abstract: Glucocorticoid-induced TNF receptor-related protein (GITR) is expressed in regulatory T cells at high levels, but is also inducible in conventional effector T cells after activation. Initial studies using an agonistic anti- GITR mAb mislead this line of research with respect to the contribution of GITR stimulation on the function of regulatory T cells. In fact, GITR acts as a costimulatory receptor for both effector and regulatory T cells by enhancing effector and regulatory functions, respectively. Unlike other costimulatory ligands, GITR ligand (GITRL) expression on mature myeloid dendritic cells (DCs) is extremely limited and the GITR-GITRL pathway does not contribute markedly to direct interactions with T cells and antigen-presenting cells in the secondary lymphoid tissues. Rather, GITRL is constitutively expressed on parenchymal tissue cells and interacts with GITR expressed on tissue-infiltrating macrophages and DCs, or effector and regulatory T cells. Interactions with GITR and GITRL at local inflammatory sites induce site-specific production of cytokines and chemokines, resulting in control activation of tissue-infiltrating effector or regulatory cells and their migration. This review summarizes recent reports on the GITR-GITRL pathway, which controls both innate and adaptive immune responses.
authors.affiliation: Department of Molecular Immunology, Tokyo Medical and Dental Univerisity, Graduate School, Tokyo, Japan. miyuki.mim@tmd.ac.jp
authors.forename: Miyuki
authors.initials: M
authors.lastname: Azuma
mesh_terms: D056704:Adaptive Immunity; D000818:Animals; D053450:Glucocorticoid-Induced TNFR-Related Protein / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007113:Immunity, Innate; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology; D048069:Tumor Necrosis Factors / Q000276:immunology*
chemical_list: D053450:Glucocorticoid-Induced TNFR-Related Protein; D048069:Tumor Necrosis Factors