GITR Fc Chimera, Human

GITR (glucocorticoid-induced tumor necrosis factor receptor), also known as AITR and TNFRSF18, is a 40 kDa transmembrane glycoprotein that functions in immune regulation. Mature human GITR consists of a 137 amino acid extracellular domain (ECD) with three tandem TNFR cysteine-rich repeats, a 21 aa transmembrane segment, and a 58 aa cytoplasmic domain. Within the ECD, human GITR shares 55% and 60% aa sequence identity with mouse and rat GITR, respectively. Alternative splicing generates an isoform with a short deletion in the cytoplasmic domain and a potentially secreted isoform that is substituted within the third TNFR repeat and lacks the transmembrane and cytoplasmic regions. GITR is expressed on CD4+ CD25+ regulatory T cells (Treg) as well as on subsets of thymocytes, lymph node cells, and splenocytes, and it is upregulated on antigen-activated conventional CD4+ and CD8+ T cells. GITR binding by GITR Ligand/TNFSF18 costimulates the proliferation and activation of CD4+ or CD8+ conventional T cells. It also induces the proliferation of Treg but inhibits the ability of Treg to suppress immune responses. This can result in the development of autoimmunity, increased tumor cell killing by effector T cells, and increased inflammation in arthritis, allergic asthma, and inflammatory bowel disease. GITR is also expressed on sympathetic neurons where it enhances NGF-induced neurite outgrowth and branching.