%0 Journal Article %A Azuma, Miyuki %D 2010 %I Begell House %K effector T cells, GITR, GITRL, inflammation, regulatory T cells %N 6 %P 547-557 %R 10.1615/CritRevImmunol.v30.i6.40 %T Role of the Glucocorticoid-Induced TNFR-Related Protein (GITR)-GITR Ligand Pathway in Innate and Adaptive Immunity %U https://www.dl.begellhouse.com/journals/2ff21abf44b19838,7bdc9a133b3ff311,0f04b58c6232feb2.html %V 30 %X 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. %8 2010-12-09