Glucocorticoid-induced tumor necrosis factor receptor–related protein (GITR)

Glucocorticoid-induced tumor necrosis factor receptor–related protein (GITR), also known as tumor necrosis factor receptor superfamily member 18 (TNFRSF18), is a type I transmembrane protein and a member of the TNF receptor superfamily[1][3][5]. GITR is constitutively expressed on regulatory T cells (Tregs) and is upregulated on all T cell subsets upon activation, as well as being present on other immune cells such as neutrophils, NK cells, and eosinophils[1][4]. Its ligand, GITRL, is expressed on antigen-presenting cells and endothelial cells[1][5]. GITR functions as a co-stimulatory receptor, crucial in T cell activation, proliferation, and cytokine production, and it modifies both the development and suppressive activity of Tregs[1][3]. GITR signaling recruits TRAF family members and mediates downstream effects through the NF-κB and MAPK pathways[1]. GITR has significant roles in autoimmunity, cancer immunotherapy (as an immune checkpoint molecule), and inflammatory diseases such as rheumatoid arthritis and atherosclerosis[1][2]. Agonistic antibodies to GITR are under clinical investigation, particularly in combination with other immunotherapies[1]. GITR expression is being investigated as a biomarker for Tregs and for cardiovascular disease[1].

Other names

Tumor necrosis factor receptor superfamily member 18TNFRSF18CD357Activation-inducible TNFR family receptor (AITR)

- Modulation of Treg and effector T cell function via co-stimulation - Lowering CD28 activation threshold in CD8+ T cells - Inhibition of Treg suppressive capacity - Promotion of cytokine and chemokine production by immune cells - Induction of cell adhesion molecules (e.g., ICAM-1)