Tumor necrosis factor ligand superfamily member 18 (TNFSF18) (GITRL)

Tumor necrosis factor ligand superfamily member 18 (TNFSF18), commonly known as GITR ligand (GITRL), is a type II transmembrane protein that serves as the primary ligand for the glucocorticoid-induced TNFR-related protein (GITR). It is predominantly expressed on antigen-presenting cells, such as dendritic cells, macrophages, and B cells, as well as on endothelial cells. The interaction between GITRL and its receptor, GITR, provides a critical co-stimulatory signal that enhances the activation, proliferation, and survival of effector T cells while simultaneously abrogating the suppressive function of regulatory T cells (Tregs). This dual mechanism makes the GITR-GITRL pathway a significant target in immuno-oncology, where agonists are used to stimulate anti-tumor immunity. Beyond its role in cancer, GITRL is involved in the pathogenesis of autoimmune and inflammatory diseases, where its overactivity can lead to tissue damage, making it a target for antagonistic therapies. Additionally, GITRL can engage in reverse signaling, influencing the function of the ligand-bearing cells themselves, such as promoting a pro-inflammatory phenotype in macrophages.

Other names

GITRLTNFSF18AITRLTL6hGITRLGlucocorticoid-induced TNF-related ligandActivation-inducible TNF-related ligand

Agonism (mimicking natural ligand to activate GITR signaling) and Antagonism (blocking GITRL-GITR interaction)