The Role of CXCR3 in Neurological Diseases

Zhou, Ya-Qun; Liu, Dai-Qiang; Chen, Shu-Ping; Sun, Jia; Zhou, Xue-Rong; Xing, Cui; Ye, Da-Wei; Tian, Yu-Ke

With the substantial prolongation of average life expectancy, the prevalence of neurological diseases increase markedly in the past decades, leading them to become a major public health problem [1, 2] . Unfortunately, few drugs are currently available to cure these diseases. Thus, new drugs for various neurological disorders are in desperate need. Chemokines are important modulators of neuroinflammation and neurodegenerative processes [3, 4] . These small proteins are important in the activation and migration *Address correspondence to these authors at the Cancer Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; Tel: [phone]; Fax: [phone]; E-mail: [e-mail] and Department of Obstetrics & Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; Tel: [phone]; Fax: [phone]; E-mail: [e-mail] of immune cells to lesion sites [5] . The chemokine receptor CXCR3, which belongs to the CXC chemokine receptor family, is a G protein-coupled receptor that plays a vital role in mediating chemotactic migration, cell proliferation, and survival [6] [7] [8] . CXCR3 is mainly expressed by various effector T lymphocytes including CD4 + Th1 cells, CD8 + cytotoxic T cells, and natural killer (NK) cells [9, 10]. The principle chemokine ligands of CXCR3 are CXCL4, CXCL9, CXCL10 and CXCL11 [11] [12] [13] [14] . CXCL4, a plateletderived CXCR3 ligand, is weakly chemotactic for neutrophils, monocytes and fibroblasts [15] . Mainly induced by interferon gamma (IFN-γ), CXCL9, CXCL10 and CXCL11 are potent chemoattractants for monocytes, T cells, NK cells and dendritic cells. Although they share the same chemokine receptor CXCR3, these three ligands are regulated by unique promoters and exhibit distinct temporal and spatial expression patterns ( Table 1) . Recent studies have shown that the chemokine receptor CXCR3 was expressed in central nerv-ous system (CNS) diseases and involved in their pathogenesis [16] [17] [18] [19] [20] . It was shown that the expression levels of CXCR3 and its ligands were elevated in the periphery blood and cerebrospinal fluid (CSF) of patients with neurological diseases [21] [22] [23] , and were correlated with prognosis in certain cases [24] . Additionally, treatment with CXCR3 antagonists could alleviate bone cancer pain (BCP) induced mechanical allodynia [25] . These studies suggested an important role of CXCR3 in neurological diseases, indicating that targeting CXCR3 may reveal novel therapeutic interventions for the management of neurological diseases. Thus, here we summarize the current evidence supporting a role of CXCR3 in the pathogenesis of neurological diseases, including multiple sclerosis, glioma, Alzheimer's disease, chronic pain and human T-lymphotropic virus type 1-associated myelopathy.