title: GITR: a modulator of immune response and inflammation.
abstract: Glucocorticoid-Induced TNFR-Related (GITR) protein belongs to Tumor Necrosis Factor Receptor Superfamily (TNFRSF) and stimulates both the acquired and innate immunity. It is expressed in several cells and tissues, including T and Natural Killer (NK) cells and is activated by its ligand, GITRL, mainly expressed on Antigen Presenting Cells (APCs) and endothelial cells. GITR/GITRL system participates in the development of autoimmune/inflammatory responses and graft vs. host disease and potentiates response to infection and tumors. These effects are due to several concurrent mechanisms including: co-activation of effector T-cells, inhibition of regulatory T (Treg) cells, NK-cell co-activation, activation of macrophages, modulation of DC function and regulation of the extravasation process. In this chapter we describe: 1) the main structural features of GITR and GITRL, 2) the transduction pathways activated by GITR triggering, 3) the effects derived from GITR/GITRL system interaction, considering the interplay between the different cells of the immune system. Moreover, the potential use of GITR/GITRL modulators in disease treatment is discussed.
authors.affiliation: Dipartimento di Medicina Clinica e Sperimentale, Sezione di Farmacologia, Università di Perugia, Via del Giochetto, 06100, Perugia, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Nocentini
authors.forename: Carlo
authors.initials: C
authors.lastname: Riccardi
mesh_terms: D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology* / Q000628:therapy; D053450:Glucocorticoid-Induced TNFR-Related Protein; D006801:Humans; D007249:Inflammation / Q000276:immunology* / Q000473:pathology; D017475:Receptors, Nerve Growth Factor / Q000378:metabolism*; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism*
chemical_list: D053450:Glucocorticoid-Induced TNFR-Related Protein; D017475:Receptors, Nerve Growth Factor; D018124:Receptors, Tumor Necrosis Factor; C491405:TNFRSF18 protein, human; C106544:Tnfrsf18 protein, mouse