Researchers in Zizhen Kang, PhD’s research laboratory, in collaboration with Ashutosh Mangalam, PhD’s research laboratory, have discovered that oligodendroglial lineage cells (OLCs)—traditionally known for producing myelin—actively contribute to neuroinflammation in experimental autoimmune encephalomyelitis (EAE), a widely used model for multiple sclerosis (MS).

Using a cutting-edge RiboTag RNA sequencing approach, the team profiled ribosome-bound mRNAs specifically from OLCs during early disease. They identified 1,556 genes upregulated and 683 genes downregulated in OLCs from EAE mice compared to healthy controls. The upregulated genes were enriched in immune pathways, including cytokine signaling, interferon responses, and antigen presentation, while downregulated genes were linked to myelination and neuronal development.

Functional studies revealed that interferon-gamma (IFN-γ) signaling within OLCs promotes disease severity by enhancing antigen presentation and inflammatory chemokine production, whereas interferon-beta (IFN-β) signaling in OLCs appeared less critical. The team also identified new cytokine receptors on OLCs and showed that IL-4 and IL-13 promote, while IL-3 and IL-21 inhibit, oligodendrocyte maturation.

This work highlights OLCs as active participants in neuroinflammation and potential therapeutic targets in MS and related disorders. By revealing cell-type–specific inflammatory programs, the study opens new avenues for developing treatments aimed at modulating OLC responses to protect myelin and support repair.

The full study was published in the Journal of Neuroinflammation. Read the full story here.