MS as a disease of immaturity

Multiple sclerosis (MS) lesions are characterized by loss of myelin, the insulating coat that surrounds axons. This is despite an abundance of the myelin-supplying glial cells called oligodendrocytes around the lesion. Gareth John, Celia Brosnan, and colleagues (Albert Einstein College of Medicine, Bronx, NY) now provide evidence that an inflammatory cascade keeps those oligodendrocytes in an immature state that does not allow for myelin production.

John started out by adding together two elements present in MS lesions: various immune molecules and glial cells called astrocytes. One change stood out: the cytokine TGFβ1 caused astrocytes to make Jagged1. This ligand for Notch (which is present on oligodendrocytes) was also made by reactive astrocytes in MS lesions. Addition of Jagged1 to cultured oligodendrocytes inhibited process outgrowth, which is one measure of maturation.

During development, Jagged1 keeps oligodendrocytes in an...