TNFRSF18/GITR/CD357

TNFRSF18/GITR/CD357 encodes a type I TNF receptor superfamily protein that inhibits TCR-induced apoptosis and functions as an activation-inducible costimulatory receptor for T cells^[1][2]. Mechanistically, GITR engages GITRL and uses TRAF-dependent signaling to regulate NF-κB activity, T-cell activation, proliferation, cytokine production, and programmed cell death^[2][3][4]. In immune regulation, GITR supports thymic regulatory T-cell differentiation and marks activated or functional Treg populations, linking the TNFRSF18/GITR/CD357 pathway to immune tolerance and inflammation models^[5]. Compared with full-length GITR, reported GITR splice variants provide an isoform-level distinction that should be considered when designing assays, antibodies, or expression studies^[6]. Structural studies further show that human and mouse GITR-GITRL complexes share receptor-ligand and receptor-receptor interfaces but form distinct higher-order assemblies, supporting species-aware experimental design^[7]. For experimental applications, agonistic anti-GITR antibody DTA-1 altered regulatory T-cell stability and intratumor accumulation in B16 melanoma models, making GITR agonism useful for studying tumor immune suppression and Treg biology^[8].