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Tumor necrosis factor receptor superfamily member 18 (TNFRSF18) also known as activation-inducible TNFR family receptor (AITR)[1] or glucocorticoid-induced TNFR-related protein (GITR) is a protein that in humans is encoded by the TNFRSF18 gene.[2][3][4] 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.[4]


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.[5]


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 .[6]

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.[7]


  1. Kim YS, Jung HW, Choi J, Kwon BS, Ham SY, Jung AK, Ko BK (Nov 2007). "Expression of AITR and AITR ligand in breast cancer patients". Oncol Rep. 18 (5): 1189–94. doi:10.3892/or.18.5.1189. PMID 17914571.
  2. Nocentini G, Giunchi L, Ronchetti S, Krausz LT, Bartoli A, Moraca R, Migliorati G, Riccardi C (Jul 1997). "A new member of the tumor necrosis factor/nerve growth factor receptor family inhibits T cell receptor-induced apoptosis". Proc Natl Acad Sci U S A. 94 (12): 6216–21. doi:10.1073/pnas.94.12.6216. PMC 21029. PMID 9177197.
  3. Kwon B, Yu KY, Ni J, Yu GL, Jang IK, Kim YJ, Xing L, Liu D, Wang SX, Kwon BS (Mar 1999). "Identification of a novel activation-inducible protein of the tumor necrosis factor receptor superfamily and its ligand". J Biol Chem. 274 (10): 6056–61. doi:10.1074/jbc.274.10.6056. PMID 10037686.
  4. 4.0 4.1 "Entrez Gene: TNFRSF18 tumor necrosis factor receptor superfamily, member 18".
  5. Park MS, Lee HM, Hahn SB, Moon SH, Kim YT, Lee CS, Jung HW, Kwon BS, Riew KD (Oct 2007). "The Association of the Activation-Inducible Tumor Necrosis Factor Receptor and Ligand with Lumbar Disc Herniation". Yonsei Med J. 48 (5): 839–46. doi:10.3349/ymj.2007.48.5.839. PMC 2628152. PMID 17963343.
  6. Yifan Zhan; David P. Funda; Alison L. Every; Petra Fundova; Jared F. Purton; Douglas R. Liddicoat; Timothy J. Cole; Dale I. Godfrey; Jamie L. Brady; Stuart I. Mannering; Leonard C. Harrison; Andrew M. Lew (2004). "TCR-mediated activation promotes GITR upregulation in T cells and resistance to glucocorticoid-induced death". International Immunology. 16 (9): 1315–1321. doi:10.1093/intimm/dxh134. PMID 15262900.
  7. Shimizu J, Yamazaki S, Takahashi T, Ishida Y, Sakaguchi S (February 2002). "Stimulation of CD25(+)CD4(+) regulatory T cells through GITR breaks immunological self-tolerance". Nat. Immunol. 3 (2): 135–42. doi:10.1038/ni759. PMID 11812990.

Further reading

This article incorporates text from the United States National Library of Medicine, which is in the public domain.