Crosstalk Between Oligodendrocyte Lineage Cells and CNS ‐Resident and Peripheral Immune Cells Governs Demyelination and Remyelination in Multiple Sclerosis

ABSTRACT Multiple sclerosis (MS) is an autoimmune neurodegenerative disease characterized by immune‐mediated attacks on myelin produced by oligodendrocytes (OLs). Oligodendrocyte precursor cells (OPCs) and mature OLs are CNS cell types essential for generating myelin sheath, which supports saltatory conduction and neuronal metabolic support. Although the roles of CNS resident cells (neurons, microglia, astrocytes) and peripheral immune cells in MS pathogenesis are well established, our understanding of how oligodendrocyte lineage cells (OLCs)—comprising OPCs and mature OLs—bidirectionally interact with these cell types to influence disease progression remains incomplete. Emerging evidence emphasizes the critical role of disease‐associated OLCs in neuroimmune responses and their underlying signaling mechanisms. Therefore, elucidating how pathological environments shaped by CNS and peripheral cells influence OLC function may identify critical therapeutic targets for promoting remyelination and recovery in MS. This review synthesizes current knowledge of OLC biology in health and disease, with emphasis on complex intercellular interactions that determine demyelination, remyelination, and axonal integrity in MS.