Efferocytosis: a novel therapeutic approach to combat disease progression in a mouse model of Multiple Sclerosis 3163

Abstract Description Efferocytosis, the process of cellular clearance by phagocytes like macrophages, is essential for tissue homeostasis. Impairment of this process has been linked to chronic inflammatory diseases. Multiple sclerosis (MS) is an autoimmune disease characterized by the accumulation of myelin debris and dead cells in the CNS. While the exact role of efferocytosis in MS remains unclear, we investigated the role of efferocytosis in MS using its preclinical mouse model, experimental autoimmune encephalomyelitis (EAE). We found that macrophages and microglia from EAE mice exhibited significantly reduced efferocytic capacity compared to controls. This impairment was associated with downregulation of key efferocytosis receptors, including Mertk, Axl, and ELMO. To explore the therapeutic potential of enhancing efferocytosis, we injected EAE mice with apoptotic cell-primed macrophages. This intervention resulted in delayed disease onset, reduced clinical severity, and decreased infiltration of pathogenic CD4+ T cells into the central nervous system (CNS). Additionally, metabolic profiling using Seahorse and SCENITH assays indicated that efferocytotic macrophages switched towards oxidative phosphorylation, suggesting improved mitochondrial function. Our findings highlight the critical role of efferocytosis in regulating immune responses and disease progression in EAE. Enhancing efferocytosis may represent a novel therapeutic strategy for MS and other chronic inflammatory diseases. Topic Categories Therapeutic Approaches to Autoimmunity (THER)