GITRL/AITRL

GITRL (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). GITR/GITRL interaction plays a role in the pathogenesis of tumor, inflammation, as well as autoimmune diseases^[1]. 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^[2]. 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^[3]. Human GITRL shares < 55% common aa identity with mouse. Human GITRL consists of cytoplasmic domain (M1-W27), helical domain (L28-F48), and extracellular domain (L49-S177). Human GITRL is a trimer, but can also be a monomer or assemble in other multimeric structures, but murine GITRL is a dimer^[4].