Positive feedback loop via astrocytes causes chronic inflammation in virus-associated myelopathy

摘要: Human T-lymphotropic virus type 1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a rare neurodegenerative disease characterized by chronic inflammation in the spinal cord. We hypothesized that positive feedback loop driven chemokines may be responsible for HAM/TSP. aimed to determine identity of these chemokines, where they are produced, and how drive found patients with HAM/TSP have extraordinarily high levels chemokine CXCL10 (also known as IP-10) an abundance cells expressing CXCL10-binding receptor CXCR3 cerebrospinal fluid. Histological analysis revealed astrocytes main producers cords Co-culture human astrocytoma CD4+ T from produce response IFN-γ secreted cells. Chemotaxis assays results suggest induces migration peripheral blood mononuclear central nervous system anti-CXCL10 neutralizing antibody can disrupt this migration. In short, we inferred 1-infected secrete CXCL10, which recruits more infected area via CXCR3, constituting helper 1-centric inflammation.