Oligodendroglia as Active Immunomodulators in Demyelinating Diseases

Oligodendrocytes (OLs) and oligodendrocyte progenitor cells (OPCs) are essential central nervous system (CNS) cell types responsible for myelin formation, efficient signal conduction, and axonal homeostasis. While the immunological functions of other glial cells-microglia and astrocytes-are well established, the involvement of oligodendrocyte lineage cells (OLCs) in the CNS inflammation has only recently gained recognition. Under pathological conditions, particularly during demyelination, OLCs transition into disease-associated states characterized by the release of pro- and anti-inflammatory chemokines and cytokines once thought to be exclusive to immune cells, thereby challenging their traditional characterization as passive victims. Elucidating the precise immunomodulatory roles of OLCs within the neural microenvironment may be pivotal for promoting regeneration following neuroinflammation in demyelinating CNS diseases. This review focuses on the immunological profiles of OLCs, the mechanisms driving their immunomodulatory phenotypes, their interactions within the neural microenvironment, and the implications of these processes in both physiological and pathological contexts.