CXCR6

CXCR6 is a class A GPCR that binds CXCL16, mediating leukocyte adhesion through transmembrane CXCL16 and migration through soluble CXCL16^[1]. Mechanistically, the CXCL16/CXCR6 axis activates Akt, MAPK, and context-specific inflammatory programs in epithelial, immune, and tumor models^[2][3]. In intestinal inflammation, CXCR6-expressing cells respond to CXCL16, and CXCL16 expression increases in Crohn’s disease tissues and inflammatory mouse models^[2]. In liver injury models, CXCR6-dependent hepatic NKT cell accumulation promotes inflammatory cytokine production and liver fibrosis^[4]. In CNS viral recovery, CXCL16/CXCR6 maintains CD8+ tissue-resident T cells, glial activation, and ongoing synapse elimination^[5]. Compared with related chemokine receptors, CXCR6 carries a DRF motif rather than the typical DRY motif, supporting adhesion and cell retention while reducing chemotactic response^[1]. For experimental applications, CXCR6 blockade or CXCL16 targeting can test tissue-resident T-cell maintenance, inflammatory recruitment, fibrosis progression, and tumor-immune interactions^[4][5][6].