CXC motif chemokine receptor 3 (CXCR3)

CXCR3 is a G protein-coupled receptor (GPCR) belonging to the CXC chemokine receptor family. It is primarily expressed on activated T lymphocytes, especially Th1-type CD4+ T cells and effector CD8+ T cells, as well as on other immune cell subsets such as regulatory T cells (Tregs), natural killer (NK) cells, and some tissue-resident pericytes. CXCR3 binds three main interferon-inducible chemokines: CXCL9 (MIG), CXCL10 (IP-10), and CXCL11 (I-TAC). Upon ligand binding, it induces integrin activation, cytoskeletal rearrangement, chemotactic migration, and intracellular calcium mobilization in target immune cells. Dysregulated or excessive activity involving the CXCL9/10/11–CXCR3 axis has been implicated in numerous diseases, including autoimmune disorders, chronic inflammatory diseases, transplant rejection, skin conditions, and cancer. Therapeutically targeting this axis—either blocking or enhancing specific interactions—is under investigation for treating these conditions.

CXCR3 antagonists (under development) aim to block the binding of CXCL9, CXCL10, and CXCL11 to CXCR3, thereby inhibiting leukocyte trafficking and reducing inflammation. CXCR3 agonists are also being investigated to promote tissue repair by stimulating pericyte recruitment.