ScholarWorks@성균관대학교

초록

Multiple sclerosis is an autoimmune disease characterized by numerous immune cells, including neutrophils, infiltrating the central nervous system. Previous reports point to a complex role for neutrophils in experimental autoimmune encephalomyelitis (EAE), where their heterogeneity remains poorly understood. In this study, we identified a unique population of neutrophils expressing SiglecF in the brain during EAE that can influence T cell activity. These neutrophils produced elevated levels ofTh17-polarizing cytokines, including IL-6, IL-1 beta, IL-23, and TNF-alpha, both in vivo and in vitro. Consistent with this cytokine profile, co-culturing SiglecF+ neutrophils with CD4+ T cells promoted Th17 and GM-CSF+ pathogenic Th17 differentiation and proliferation while reducing regulatory T cell numbers. Depleting SiglecF+ neutrophils with anti-SiglecF Abs reduced the severity of EAE, decreased the Th17 population, and increased the regulatory T cell population in the brain. These findings suggest that SiglecF+ neutrophils promote autoimmune neuroinflammation by reinforcing pathogenic autoreactive Th17 cell responses.

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