CHEMOKINES, CXC | CXCL9 (MIG)

Human CXCL9 was identified in 1993 by a differential hybridization screening technique, comparing cDNA libraries obtained from an unstimulated and interferon gamma (IFN-γ)-activated macrophage cell line. CXCL9 is a member of the alpha or CXC subfamily of chemokines. The CXC chemokines can be subdivided based on the presence or absence of a tripeptide motif Glu–Leu–Arg (ELR) N-terminal to the conserved CXC region. CXCL9, a non-ELR-containing CXC chemokine, mediates most of its biological function through binding to CXCR3, a seven-transmembrane-domain receptor coupled to G proteins. CXCL9 primarily attracts activated T lymphocytes, preferentially of the Th1 phenotype, which express high levels of CXCR3. The expression of CXCL9 is induced primarily by the Th1-associated cytokine IFN-γ and correlates with tissue infiltration of T lymphocytes in a number of Th1-associated diseases, suggesting that CXCL9 plays an important role in the regulation of effector cell recruitment to sites of inflammation. Remarkably, CXCL9 also regulates eosinophil accumulation in experimental asthma, a Th2-associated lung disease. In addition, CXCL9 has potent angiostatic activity, inhibiting blood vessel growth in wound repair and inhibiting tumor growth and tumor-associated vessel expansion.