title: Glucocorticoid-induced tumour necrosis factor receptor-related protein: a key marker of functional regulatory T cells.
abstract: Glucocorticoid-induced tumour necrosis factor receptor-related protein (GITR, TNFRSF18, and CD357) is expressed at high levels in activated T cells and regulatory T cells (Tregs). In this review, we present data from mouse and human studies suggesting that GITR is a crucial player in the differentiation of thymic Tregs (tTregs), and expansion of both tTregs and peripheral Tregs (pTregs). The role of GITR in Treg expansion is confirmed by the association of GITR expression with markers of memory T cells. In this context, it is not surprising that GITR appears to be a marker of active Tregs, as suggested by the association of GITR expression with other markers of Treg activation or cytokines with suppressive activity (e.g., IL-10 and TGF-β), the presence of GITR(+) cells in tissues where Tregs are active (e.g., solid tumours), or functional studies on Tregs. Furthermore, some Treg subsets including Tr1 cells express either low or no classical Treg markers (e.g., FoxP3 and CD25) and do express GITR. Therefore, when evaluating changes in the number of Tregs in human diseases, GITR expression must be evaluated. Moreover, GITR should be considered as a marker for isolating Tregs.
authors.affiliation: Section of Pharmacology, Department of Medicine, University of Perugia, Piazza Severi 1, 06132 Perugia, Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: Ronchetti
authors.affiliation: Section of Pharmacology, Department of Medicine, University of Perugia, Piazza Severi 1, 06132 Perugia, Italy.
authors.forename: Erika
authors.initials: E
authors.lastname: Ricci
authors.affiliation: Section of Pharmacology, Department of Medicine, University of Perugia, Piazza Severi 1, 06132 Perugia, Italy.
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Petrillo
authors.affiliation: Section of Pharmacology, Department of Medicine, University of Perugia, Piazza Severi 1, 06132 Perugia, Italy.
authors.forename: Luigi
authors.initials: L
authors.lastname: Cari
authors.affiliation: Section of Pharmacology, Department of Medicine, University of Perugia, Piazza Severi 1, 06132 Perugia, Italy.
authors.forename: Graziella
authors.initials: G
authors.lastname: Migliorati
authors.affiliation: Section of Pharmacology, Department of Medicine, University of Perugia, Piazza Severi 1, 06132 Perugia, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Nocentini
authors.affiliation: Section of Pharmacology, Department of Medicine, University of Perugia, Piazza Severi 1, 06132 Perugia, Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: Riccardi
mesh_terms: D000818:Animals; D015415:Biomarkers; D002454:Cell Differentiation / Q000276:immunology; D049109:Cell Proliferation; D053450:Glucocorticoid-Induced TNFR-Related Protein / Q000378:metabolism*; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D050378:T-Lymphocytes, Regulatory / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism
chemical_list: D015415:Biomarkers; D053450:Glucocorticoid-Induced TNFR-Related Protein; C491405:TNFRSF18 protein, human; C106544:Tnfrsf18 protein, mouse