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

Human T-lymphotropic virus type 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a rare neurodegenerative disease characterized by chronic inflammation in the spinal cord [94, 95] . Recently, Ando et al. [96] investigated the possible role of CXCL10/CXCR3 signaling in chronic inflammation of HAM/TSP. They found that the expression level of CXCL10 was markedly high in the CSF of HAM/TSP patients and a great deal of CSF cells expressed the CXCL10-binding receptor CXCR3, which mainly consist of CD3 + cells (>90%) and small populations of CD14 + and CD19 + cells. Their immunofluorescence results showed that astrocytes were the major producers of CXCL10 in the spinal cords of HAM/TSP patients. Coculture of human astrocytoma cells with CD4 + T cells from HAM/TSP patients revealed that astrocytes produce CXCL10 in response to IFN-γ secreted by CD4 + T cells. Moreover, the chemotaxis assays results suggested that CXCL10 induced migration of peripheral blood mononuclear cells to the CNS and that anti-CXCL10 neutralizing antibody could disrupt this migration. These results demonstrated that HTLV-1 infected cells in the CNS produced IFN-γ that induces astrocytes to secrete CXCL10, which recruits more infected cells to the area via CXCR3, constituting a T helper type 1-centric positive feedback loop that results in chronic inflammation.