Meninges are a system of three-layered membranes which envelop the Central Nervous System (CNS) at each level of its organization, acting as a protective barrier. Beside this acknowledged role, meninges have emerged as complex structures able to sense, integrate and respond to CNS, external stimuli and injury. Recently, meninges have been suggested as a novel neurogenic niche hosting neural progenitors (NPCs) which can migrate and integrate into the brain cortex. However, their contribution to brain autoimmune disease is still unknown. We aimed to assess the role of meningeal neural progenitors in a paradigm of animal model of experimental autoimmune encephalomyelitis (EAE). We characterized the meningeal NPCs at different stages of the pathology by combining immunofluorescence and single cells transcriptomic analysis (scRNA). Meningeal neural progenitors respond to EAE progression by increasing their number, differentiation and migratory properties. Interestingly, we found meningeal neural progenitors in close contact with immune cells and infiltrating in the brain parenchyma. scRNA highlighted the different cellular population involved in the EAE pathogenesis including immune cells, endothelial cells, pericytes, and stromal cells. Moreover, through a ligand-receptor analysis, we were able to identify a potential crosstalk between stromal cells (i.e. neural cells) and immune cells. These results revealed that NPCs residing in meningeal structure actively respond to pathogenesis and progression of EAE, that may uncover novel cellular and molecular mechanisms to be exploited as pharmacological targets for autoimmune diseases treatment.