|Tumor necrosis factor receptor superfamily, member 18|
|Symbols||; AITR; CD357; GITR; GITR-D|
|External IDs||IUPHAR: GeneCards:|
Tumor necrosis factor receptor superfamily member 18 (TNFRSF18) also known as activation-inducible TNFR family receptor (AITR) or glucocorticoid-induced TNFR-related protein (GITR) is a protein that in humans is encoded by the TNFRSF18 gene. GITR is currently of interest to immunologists as a co-stimulatory immune checkpoint molecule.
TNFRSF18 is a member of the tumor necrosis factor receptor (TNF-R) superfamily. This receptor has been shown to have increased expression upon T-cell activation, and it is thought to play a key role in dominant immunological self-tolerance maintained by CD25+/CD4+ regulatory T cells. Knockout studies in mice also suggest the role of this receptor is in the regulation of CD3-driven T-cell activation and programmed cell death. Three alternatively spliced transcript variants of this gene encoding distinct isoforms have been reported.
Human activation-inducible tumor necrosis factor receptor (AITR) and its ligand, AITRL, are important costimulatory molecules in the pathogenesis of autoimmune diseases. Despite the importance of these costimulatory molecules in autoimmune disease, their role in the autoimmune reaction to herniated disc fragments has yet to be explored.
GITR was identified as a new member of the TNF receptor superfamily, by comparing gene expression in untreated and DEX-treated murine T-cell lines. GITR can also be induced when T cells are activated. Although mouse GITR is induced by either GC engagement or T-cell activation, its human homologue (hGITR/AITR) is upregulated only by activation. Therefore, the requirements for GR signaling in inducing GITR expression by T cells remain moot .
GITR (glucocorticoid-induced tumor necrosis factor receptor) is a surface receptor molecule that has been shown to be involved in inhibiting the suppressive activity of T-regulatory cells and extending the survival of T-effector cells. In mouse models, GITR was initially noted to be selectively enriched on the surface of regulatory T cells, making this an attractive potential surface marker for these rare cells. However, subsequent studies revealed GITR to also be up-regulated on any activated T cells in humans, thus undermining its utility as a regulatory T cell marker.
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- "Entrez Gene: TNFRSF18 tumor necrosis factor receptor superfamily, member 18".
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- Clark HF, Gurney AL, Abaya E, et al. (2003). "The Secreted Protein Discovery Initiative (SPDI), a Large-Scale Effort to Identify Novel Human Secreted and Transmembrane Proteins: A Bioinformatics Assessment". Genome Res. 13 (10): 2265–70. doi:10.1101/gr.1293003. PMC 403697. PMID 12975309.
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- Esparza EM, Arch RH (2005). "Glucocorticoid-induced TNF receptor, a costimulatory receptor on naive and activated T cells, uses TNF receptor-associated factor 2 in a novel fashion as an inhibitor of NF-kappa B activation". J. Immunol. 174 (12): 7875–82. doi:10.4049/jimmunol.174.12.7875. PMID 15944293.
- Baumgartner-Nielsen J, Vestergaard C, Thestrup-Pedersen K, et al. (2006). "Glucocorticoid-induced tumour necrosis factor receptor (GITR) and its ligand (GITRL) in atopic dermatitis". Acta Derm. Venereol. 86 (5): 393–8. doi:10.2340/00015555-0118. PMID 16955181.
- Baltz KM, Krusch M, Bringmann A, et al. (2007). "Cancer immunoediting by GITR (glucocorticoid-induced TNF-related protein) ligand in humans: NK cell/tumor cell interactions". FASEB J. 21 (10): 2442–54. doi:10.1096/fj.06-7724com. PMID 17360848.
- Lahey TP, Loisel SD, Wieland-Alter W (2007). "Glucocorticoid-Induced Tumor Necrosis Factor Receptor Family–Related Protein Triggering Enhances HIV-Specific CD4+ T Cell Cytokine Secretion and Protects HIV-Specific CD4+ T Cells from Apoptosis". J. Infect. Dis. 196 (1): 43–9. doi:10.1086/518613. PMC 2872147. PMID 17538882.
- Coe D, Begom S, Addey C, White M, Dyson J, Chai JG (2010). "Depletion of regulatory T cells by anti-GITR mAb as a novel mechanism for cancer immunotherapy.". Can. Immunol. Imm. 59 (9): 1367–77. doi:10.1007/s00262-010-0866-5. PMID 20480365.
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