Role of CXCL10 in central nervous system inflammation

Abstract

Role of CXCL10 in central nervous system inflammation Daniela Michlmayr, Clive S McKimmie Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, Scotland, UK Abstract: The central nervous system (CNS) is a highly complex tissue that is vital for a large number of life-dependent processes. The neurons of the CNS are post-mitotic and cannot be easily replaced or repaired if lost or damaged. The hallmark of neuroinflammation is an influx of leukocytes through the blood–brain barrier or blood–cerebrospinal fluid barrier. Depending on the disease, the presence of leukocytes can have beneficial or detrimental effects on disease outcome. Importantly, the entry of leukocytes into the CNS is primarily controlled by chemokines, a large family of chemotactic cytokines that coordinate the movement of leukocytes into and within tissues. Expression of inflammatory chemokines is almost absent in the resting CNS, but can be highly upregulated during inflammation. This includes CXCL10, a chemokine that has critical roles in controlling the entry of several important leukocyte subsets into the brain and other tissues. CXCL10 is expressed by neurons, glia, and stromal cells in a number of different CNS diseases and can have either a protective or a detrimental role in facilitating disease progression or resolution. CXCL10 together with CXCL9 and CXCL11 binds to CXCR3, which is predominantly expressed on activated T-cells and natural killer cells. Due to the ability of CXCL10 to mediate leukocyte influx in a variety of inflammatory CNS diseases, research has focused on identifying drugs that block the function of CXCL10 or CXCR3. Many of these drugs are under investigation and are discussed here in detail. In this paper, we review the function of CXCL10 during nervous system inflammation and highlight the latest developments that suggest its involvement in a number of key diseases, including multiple sclerosis, Alzheimer's disease, and viral encephalitis. Keywords: chemokine, neuroinflammation, neuroimmunology, encephalitis, CXCL10