Interferon Regulatory Factor 8 Drives Autoimmune Neuroinflammation in Experimental Autoimmune Encephalomyelitis

Multiple sclerosis (MS) is an immune-mediated demyelinating disease of the central nervous system. The interferon regulatory factor (IRF) family comprises transcription factors that regulate immune responses; however, their roles in MS pathogenesis remain unclear. In this study, we investigated whether IRFs are involved in MS pathology using experimental autoimmune encephalomyelitis (EAE) model mice. Among the IRFs examined, IRF8 expression was significantly increased in the spinal cord of EAE model mice and predominantly localized to myeloid cells. Consistently, patients with MS exhibited significantly increased proportions of IRF8-positive myeloid cells in peripheral blood. Notably, IRF8 knockout mice exhibited complete resistance to EAE induction. The mRNA expression levels of neuroinflammatory mediators, including interleukin IL-1β, IL-6, tumor necrosis factor-α, IL-12b, and nitric oxide synthase 2, were significantly reduced in the spinal cord of IRF8 knockout mice. Collectively, these findings suggest that IRF8 is a critical regulator of autoimmune neuroinflammation, highlighting its potential as a therapeutic target for MS.