CXCL7 aggravates the pathological manifestations of neuromyelitis optica spectrum disorder by enhancing the inflammatory infiltration of neutrophils, macrophages and microglia

Abstract

Neuromyelitis optica spectrum disorder (NMOSD) is an inflammatory demyelinating disease of the central nervous system (CNS). Our previous study indicated that neutrophil-related chemokine CXCL7 is elevated in the cerebrospinal fluid (CSF) of NMOSD patients. To study the potential function of CXCL7 during NMOSD, we measured the chemokines level in CSF of follow-up patients, and established three NMOSD mouse models by injecting aquaporin4 (AQP4)-IgG. Astrocytes loss, inflammatory infiltration, and myelin sheath damage were detected by western blot or immunofluorescence analysis. We found CXCL7 was significantly increased in the serum and CSF of model mice, and exogenous CXCL7 caused serious astrocyte injury, obvious microglia activation, and increased infiltration of neutrophils and macrophages, resulting in secondary demyelination. Consistently, knocking down the CXCL7 reversed the loss of AQP4, and attenuated the inflammatory response. Collectively, our data indicates that CXCL7 aggravates NMOSD-like pathological damage to astrocytes and myelin sheath mainly via promoting neuroinflammatory response.