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Central nervous system (CNS) inflammation is a key factor in multiple sclerosis (MS). Invasion of peripheral immune cells into the CNS resulting from an unknown signal or combination of signals results in activation of resident immune cells and the hallmark feature of the disease: demyelinating lesions. These lesion sites are an amalgam of reactive peripheral and central immune cells, astrocytes, damaged and dying oligodendrocytes, and injured neurons and axons. Sustained inflammation affects cells directly located within the lesion site and further abnormalities are apparent diffusely throughout normal-appearing white matter and grey matter. It is only relatively recently, using animal models, new tissue sampling techniques, and next-generation sequencing, that molecular changes occurring in CNS resident cells have been broadly captured. Advances in cell isolation through Fluorescence Activated Cell Sorting (FACS) and laser-capture microdissection together with the emergence of single-cell sequencing have enabled researchers to investigate changes in gene expression in astrocytes, microglia, and oligodendrocytes derived from animal models of MS as well as from primary patient tissue. The contribution of some dysregulated pathways has been followed up in individual studies; however, corroborating results often go unreported between sequencing studies. To this end, we have consolidated results from numerous RNA-sequencing studies to identify and review novel patterns of differentially regulated genes and pathways occurring within CNS glial cells in MS. This article is categorized under: Neurological DiseasesMolecular and Cellular Physiology.

Multiple sclerosis (MS) is a neuroinflammatory disease characterized by demyelinating plaques in the brain and spinal cord, causing progressive loss of functions. While the causes of MS remain undefined, treatments that target immune cells or their functions greatly improve the clinical outcome. Our laboratory has previously shown that production of the inflammatory cytokine interleukin (IL)-1β by myeloid cells is required for the development of experimental autoimmune encephalomyelitis (EAE), an MS model. Here, we show that activation of central nervous system (CNS) endothelial cells by IL-1β enables inflammatory monocytes to enter the CNS and differentiate into antigen-presenting cells. Additionally, we demonstrate that factors released from the interaction between IL-1β–producing myeloid cells and autoreactive CD4+ T cells are toxic to neurons.