Meningeal inflammation and multiple sclerosis

Abstract

Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system (CNS). Inflammation in MS is characterized by infiltration of peripheral immune cells into the CNS, especially in the meninges. The infiltration into meninges, which has been referred to as tertiary lymphoid tissues (TLTs), is a likely first step preceding infiltration into the CNS parenchyma. These invading autoreactive immune cells destroy myelin, the insulation surrounding neuronal axons, and cause demyelination in subpial and cortical areas, promoting disease pathogenesis. Experimental autoimmune encephalomyelitis (EAE), a widely used murine model of MS, also shares this characteristic. However, what cellular components and molecular pathways support infiltrating lymphocyte retention and production within the meninges as well as further invading into the CNS parenchyma are still not clear. Pikor et al. first reported that stromal cells in the inflamed CNS meninges (TLTs) play an important role in the neuroinflammatory process of MS. They also demonstrated that collaboration between the encephalitogenic T helper 17 (Th17) cell and lymphotoxin pathways contributes to the formation of TLTs.