The immunological role of oligodendrocytes: beyond myelin maintenance

Abstract

Oligodendrocytes (OGDs) are well-established cells in the central nervous system (CNS), primarily recognized for their role in myelination. However, emerging evidence suggests intrinsic differences among OGDs that may lead to diverse functions. OGDs heterogeneity could depend on their origin, location, age, and the presence of pathology. These variations indicate that specific populations of OGDs can modulate local immune responses and interact with other immune cells beyond their role in myelination. OGDs express major histocompatibility complex class I and class II molecules and can thus present endogenous and exogenous antigens to CD8 + and CD4 + T cells, respectively. In physiological conditions, OGDs release factors that maintain microglial quiescence and support homeostatic functions. However, during neuroinflammation, OGDs interact with microglia, astrocytes, and peripheral immune cells infiltrating the CNS, which may change their signaling profiles. In inflammatory conditions, OGDs demonstrate their active role in CNS immunology by producing a range of pro-inflammatory cytokines and chemokines. These factors are critical to the regulation of immune cell migration and activation within the CNS. Conversely, OGDs can also release anti-inflammatory factors, such as brain-derived neurotrophic factors, which help mitigate excessive inflammatory responses. Research into how OGDs affect and are affected by neighboring cells may unveil new therapeutic targets and strategies. The dual roles of OGDs in immunology and CNS function present both opportunities and challenges for advancing our understanding and treatment of CNS disorders.

Keywords: chemokines; cytokines; major histocompatibility complex; neuroinflammation; oligodendrocytes.

Figure 1.

Radial Glia cells are known to divide symmetrically or asymmetrically to produce neurons and astrocytes through several rounds of proliferation and differentiation. Following this initial wave of neurogenesis, a second wave of gliogenesis begins, leading to the production of astrocytes. In a third wave, radial glia can also differentiate into OGDs and produce intermediate OPCs which later mature into OGDs.

Figure 2.

Under physiological conditions, OGDs release factors that maintain microglial quiescent and support homeostatic functions, such as synaptic pruning and debris clearance. In contrast, during neuroinflammation, OGDs express MHC class I and class II molecules, enabling them to present endogenous and exogenous antigens to CD8 + and CD4 + T cells, respectively. Additionally, they interact with microglia cells by secreting pro-inflammatory cytokines, transforming them into a pro-inflammatory state. Moreover, the interactions between OGDs, astrocytes, and peripheral immune cells infiltrating the CNS result in altered signaling profiles. During neuroinflammation, OGDs also produce pro-inflammatory cytokines, such as TNF-α, IL-1β, and IL-6, as well as chemokines, like CCL2, CCL5, and CXCL10, which can influence the recruitment of peripheral immune cells across the blood–brain barrier amplifying the neuroinflammatory response.