Chemokine receptor CXCR3: an unexpected enigma

CXCR3, the receptor for CXCL9/MIG, CXCL10/IP-10, and CXCL11/I-TAC, is preferentially expressed on activated Th1 T cells and has been predicted to play an important role in their trafficking. However, this simplistic view of the function of CXCR3 and its ligands has not been borne out by studies of disease models, including experimental autoimmune encephalomyelitis (EAE), using varied methods of receptor blockade, as well as knockout or transgenic mice. This review focuses on the current understanding of the enigmatic role of CXCR3 and its ligands in CNS inflammatory/autoimmune disorders. The conflicting results among varied models of CNS inflammation suggest complex and multiple roles for CXCR3 and its ligands in the pathogenesis of CNS inflammatory/autoimmune diseases. Thus, further study is needed to determine how CXCL10 neutralizing agents or CXCR3 receptor antagonists might be applied to treating human disease.