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This study aimed to identify the inflammatory translatome of OLCs during the onset of experimental autoimmune encephalomyelitis (EAE), a widely used model for Multiple Sclerosis (MS), using RiboTag-based RNA sequencing. We crossed RiboTag mice with Olig2-Cre mice to obtain strain-specific expression of HA-tagged ribosomal protein Rpl22 in OLCs, enabling the isolation of ribosome-associated mRNA from these cells for sequencing by using HA beads. Compared to controls, 1,556 genes were upregulated and 683 were downregulated in EAE OLCs. Gene enrichment revealed elevated immune-related pathways, including cytokine signaling, interferon responses and antigen presentation, whereas downregulated genes were associated with myelination and neuronal development. Notably, significant expression of cytokines\/chemokines and their receptors was detected in OLCs. Further investigations focused on the role of IFNGR and IFNAR in EAE pathogenesis. IFN-\u03b3 signaling in OLCs exacerbated EAE pathogenesis by enhancing antigen processing, presentation, and chemokine production (e.g., Ccl2, Ccl7). In contrast, IFN-\u03b2 signaling appeared less critical. These findings highlight the inflammatory role of OLCs in EAE, suggesting OLCs as a potential therapeutic target for mitigating neuroinflammation in MS and related disorders.<\/jats:p>","DOI":"10.1186\/s12974-025-03463-x","type":"journal-article","created":{"date-parts":[[2025,5,21]],"date-time":"2025-05-21T07:59:30Z","timestamp":1747814370000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["RiboTag-based RNA profiling uncovers oligodendroglial lineage-specific inflammation in autoimmune encephalomyelitis: implications for pathogenesis"],"prefix":"10.1186","volume":"22","author":[{"given":"Yuhang","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sudeep","family":"Ghimire","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashutosh","family":"Mangalam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zizhen","family":"Kang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,5,21]]},"reference":[{"issue":"8","key":"3463_CR1","doi-asserted-by":"publisher","first-page":"628","DOI":"10.1016\/j.tins.2023.05.007","volume":"46","author":"J Buchanan","year":"2023","unstructured":"Buchanan J, da Costa NM, Cheadle L. 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