AITRL, a type II transmembrane protein, is a ligand for glucocorticoid-induced TNFR-related protein (GITR). GITR, a member of the TNFR superfamily, is expressed in T cells, natural killer cells and some myeloid cells. And GITRL is mainly expressed on antigen presenting cells (B cells, dendritic cells), macrophages and endothelial cells (ECs).
When GITRL binds to GITR, GITR can produce costimulatory signals that regulate T-cell proliferation and effector functions. The interaction stimulates proliferation and cytokine production of both CD4+ Teff and Treg cells, and drives antitumor activity of CD8+ T cells. Besides, GITRL plays a role in EC-activation and promotes adhesion in both mice and humans, which increases STAT-1 phosphorylation and the augmented expression of adhesion molecules such as VCAM-1 and ICAM-1.
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