GITR

GITR, short for glucocorticoid-induced TNFR-related protein, is a member of the tumor necrosis factor receptor (TNFR) superfamily. It is encoded by the TNFRSF18 gene in humans and by a homologous gene in mice. The receptor binds to its ligand, GITRL (TNFSF18), which is primarily expressed on antigen-presenting cells such as dendritic cells, macrophages, and B cells.

Expression and signaling: In mice, GITR is constitutively expressed at high levels on regulatory T cells (Tregs) and is upregulated on conventional T cells after activation. In humans, expression is low on resting T cells and increases upon activation; Tregs also express GITR. Upon engagement, GITR transmits signals via adaptor proteins including TRAF2 and TRAF5, activating NF-kB and MAP kinases, promoting T cell proliferation and cytokine production, and reducing Treg-mediated suppression under certain conditions.

Functional and clinical relevance: GITR costimulation acts as a co-stimulatory signal that can enhance effector T cell responses while modulating Treg activity, and is being explored as a target for cancer immunotherapy. GITR agonists, including monoclonal antibodies and GITRL-based constructs, are under investigation in preclinical and clinical studies to augment anti-tumor immunity; research also considers potential applications in autoimmune diseases by adjusting immune regulation.