Glial cells in chronic inflammation: diversity, dysfunction and therapeutic targeting

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS). Current therapies for relapsing MS primarily target the peripheral immune system but have consistently failed to address mechanisms underlying disease progression, which are thought to involve CNS-resident glial cells such as astrocytes, microglia and oligodendrocytes. Recent technological advances have revealed the functional heterogeneity of these glial cells, highlighting their crucial roles in inflammation, demyelination, remyelination and neurodegeneration. In this Review, we summarize emerging insights into the diversity, function and regulation of glial cells in MS and inflammation in general, highlight their interactions with immune cells and non-immune cells in the CNS, and discuss potential strategies for their therapeutic modulation.