C-X-C Chemokine Receptor Type 3 (CXCR3)

C-X-C Chemokine Receptor Type 3 (CXCR3) is a seven-transmembrane, G protein-coupled receptor (GPCR) belonging to the CXC chemokine receptor family. It is predominantly expressed on activated T lymphocytes (especially Th1-type CD4+ T cells) and effector CD8+ T cells, as well as natural killer cells and some epithelial cells. Its main ligands are CXCL9 (MIG), CXCL10 (IP-10), and CXCL11 (I-TAC), which are interferon-inducible chemokines. CXCR3 mediates trafficking of effector T cells to sites of inflammation or infection and plays a key role in amplifying Th1-type immune responses. It has a context-dependent role in cancer, with CXCR3A promoting tumor cell proliferation/migration and CXCR3B inhibiting it. Different isoforms also exhibit different binding profiles: CXCR3-A binds CXCL9, CXCL10, and CXCL11; CXCR3-B binds CXCL9, CXCL10, CXCL11, and CXCL4; and CXCR3-alt only binds CXCL11. Upon ligand binding, CXCR3 activates Gαi proteins, leading to increased intracellular Ca²⁺, activation of phosphoinositide 3‑kinase, and activation of mitogen‑activated protein kinase pathways.

Other names

G protein-coupled receptor 9GPR9CD183

Modulation of immune cell migration and activity via chemokine signaling.