Tumor necrosis factor receptor superfamily member 18 (TNFRSF18), also known as activation-inducible TNF receptor (AITR), glucocorticoid-induced tumor necrosis factor receptor family-related protein (GITR), CD357, or GITR-D, has increased expression upon T-cell activation, and is thought to play a key role in dominant immunological self-tolerance maintained by CD25(+)CD4(+) regulatory T cells []. In inflammatory cells, GITR expression indicates a possible molecular link between steroid use and complicated acute sigmoid diverticulitis; increased MMP-9 expression by GITR signaling might explain morphological changes in the colonic wall in diverticulitis []. Its ligand, GITRL, activates GITR which could then influence the activity of effector and regulatory T cells, participating in the development of several autoimmune and inflammatory diseases, including autoimmune thyroid disease and rheumatoid arthritis [, ]. In systemic lupus erythematosus (SLE) patients, serum GITRL levels are increased compared with healthy controls []. GITR and its ligand, GITRL, are possibly involved in the pathogenesis of primary Sjogren's syndrome (pSS) [].GITR is inactivated during tumor progression in Multiple Myeloma (MM); restoration of GITR expression in GITR deficient MM cells leads to inhibition of MM proliferation and induction of apoptosis, thus playing a pivotal role in MM pathogenesis and disease progression []. Regulatory T-cells (Tregs) in liver tumor up-regulate the expression of GITR compared with Tregs in tumor-free liver tissue and blood []. Regulatory single nucleotide polymorphisms (SNPs) in the promoter regions of the TNFRSF18 gene have been identified in a group of male Gabonese individuals exposed to a wide array of parasitic diseases such as malaria, filariasis and schistosomiasis, and may serve as a basis to study parasite susceptibility in association studies [].This entry represents the N-terminal domain of TNFRSF18. TNF-receptors are modular proteins. The N-terminal extracellular part contains a cysteine-rich region responsible for ligand-binding. This region is composed of small modules of about 40 residues containing 6 conserved cysteines; the number and type of modules can vary in different members of the family [, , ].
