About AITRL / GITRL:
AITRL / TNFSF18 cytokine is a member of the TNF ligand family andconstitutes as a ligand for TNFRSF18 / AITR. AITRL / TNFSF18 controls the survival of T lymphocyte in peripheral tissues. AITRL / TNFSF18 is produced in endothelial cells, and takes an essential role in T lymphocytes and endothelial cells interaction.
TNFSF18 acts decreases the threshold for T-cell activation and T-cell proliferation. Facilitates initiation of NF-kappa-B. Activates the rise in phosphorylation of STAT1 and controls the production of VCAM1 and ICAM1. AITRL increases leukocyte bonding to endothelial cells and modulates the movement of monocytes from the splenic reservoir to locations of inflammation.
TNFSF18 is produced in human and murine keratinocytes and its expression triggered by Th2 proteins in mouse keratinocytes. The stimulation of AITRL in human keratinocytes is controled by TNFA and Th2 proteins. Ligation of TNFRSF18 stimulates nuclear factor (NF)-kappa B production through TNF receptor-associated factor 2 and guards the cells from TCR activation-induced cell death.
TNFRS18 is produced small quantities in bone marrow, peripheral blood T cells, thymus, lymph nodes and spleen. The human AITR expression of is not induced by the treatment with dexamethasone as found in mouse species, but is controlled by antigen-receptor interaction or by soluble anti-CD3 and anti-CD28 or PMA with addition of ionomycin. TNFSF18 is expressed on murine splenic B cells by IL4 & CD40, LPS, CpG and oligonucleotide GITRL is also produced in retinal pigment epithelial cells by IFNG, TNFA and IL1A. TNFSF18 binds to TNFRSF18 and activates the control of the immune to tryptophan catabolism using reverse signaling in mouse dendritic cells.