GPR15L

GPR15L is a newly identified ligand for GPR15, a member of the G protein‐coupled receptor (GPCR) family. Upon ligation, GPR15L acts as a potent chemoattractant for GPR15‐expressing T cells and together they mediate lymphocyte recruitment to the large intestine and skin. GPR15L is constitutively expressed by colon epithelial cells where its expression is minimally altered by intestinal inflammation. Conversely, GPR15L is nearly undetectable in adult epidermis but highly upregulated during wound healing and inflammation, particularly in psoriasis. Significant expression of GPR15L is also seen in additional mucosal epithelial cells, including those of the stomach, esophagus, and urinary tract. While maintaining similar expression patterns and intramolecular disulfide cysteine bridges found in members of the CC chemokine family, GPR15L differs from classic CC and CXC chemokines, whose active sites are found on the N‐terminus, in that it relies on its C‐terminus for receptor interaction. GPR15L was first identified as an antimicrobial peptide (AMP) due to its broad spectrum of antimicrobial activity, a property shared with many chemokines. GPR15L binds to an additional receptor, SUSD2, and early studies have indicated that both are downregulated in colon cancer tissue resulting in inhibited colon cancer growth.