Neutrophils expressing SiglecF aggravate Th17-induced autoimmune neuroinflammation 2893

Abstract Description Multiple sclerosis (MS) 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 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 of Th17-polarizing cytokines, including IL-6, IL-1β, IL-23, and TNF-α, 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 antibodies 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. Funding Sources Supported by the Basic Science Research Program Planning (NRF-2020M3A9D3038435, RS-2024-00456194, RS-2024-00401422) through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT, and Future Planning Topic Categories Neuroimmunology (NEUR)