The Chemokine CXCL10 as a Therapeutic Target in Animal Models of Neuroinflammatory Disease
Jenny L. Hardison,
Michael T. Liu,
Thomas E. Lane,
Hans S. Keirstead.
Chemokines represent a family of over 40 small proteins that, for the most part, are secreted into the environment and function by binding to G protein-coupled receptors (GPCRs) that are expressed on many different cell types. Chemokines play an important role in many biological processes including maintenance of the organizational integrity of secondary lymphoid tissue, participation in various aspects of immune responses following infection or injury, and induction of directional migration of targeted immune cell populations to sites of inflammation. Importantly, chemokines are associated with numerous inflammatory diseases in humans including multiple sclerosis (MS) and spinal cord injury (SCI). MS is a demyelinating disease characterized by an exacerbated inflammatory response leading to immune-mediated myelin destruction. The immune system also plays a critical role in SCI; primary trauma to the adult mammalian spinal cord is immediately followed by secondary degeneration in which the inflammatory response is thought to play a detrimental role. In the central nervous system (CNS), the inflammatory response is mediated in part by T lymphocytes that are recruited by chemotactic molecules such as chemokines. We have used wellaccepted animal models of MS and SCI to provide insight into the functional role of chemokines in neuroinflammation and disease. This review summarizes studies which indicate that ablation of the T cell chemotactic CXC chemokine ligand 10 (CXCL10) results in diminished neuropathology associated with decreased immune cell infiltration into the CNS. Importantly, these findings reveal that targeting chemokines such as CXCL10 may offer a powerful therapeutic approach for the treatment of neuroinflammatory diseases.
Keywords: Chemokine, Neuroinflammation, Animal models, Multiple sclerosis, Spinal cord injury
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