{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T21:57:40Z","timestamp":1791237460564,"version":"4.1.0"},"reference-count":89,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"792","content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Transl. Med."],"published-print":{"date-parts":[[2025,4,2]]},"abstract":"<jats:p>\n                    Reproducing the pathophysiology of human multiple sclerosis (MS) in animal models is critical to identifying mechanisms triggering demyelination and to developing early intervention strategies. Here, we aimed to model overactivated Wnt (wingless-related integration site) signaling previously shown in postmortem brain tissues of patients with MS by inducing experimental autoimmune encephalomyelitis (EAE) in\n                    <jats:italic>\n                      Pdgfra\n                      <jats:sup>CreER<\/jats:sup>\n                      ;Apc\n                      <jats:sup>fl\/fl<\/jats:sup>\n                    <\/jats:italic>\n                    and\n                    <jats:italic>\n                      Olig2\n                      <jats:sup>Cre<\/jats:sup>\n                      ;Apc\n                      <jats:sup>fl\/fl<\/jats:sup>\n                    <\/jats:italic>\n                    mice. These mice have overactivated Wnt signaling in oligodendrocyte precursor cells (OPCs) because of a conditional knockout of the pathway repressor adenomatous polyposis coli (APC).\n                    <jats:italic>\n                      Pdgfra\n                      <jats:sup>CreER<\/jats:sup>\n                      ;Apc\n                      <jats:sup>fl\/fl<\/jats:sup>\n                    <\/jats:italic>\n                    EAE mice exhibited increased expression of markers for Wnt activation such as Axis inhibition protein 2 (AXIN2) and Wnt inhibitory factor 1 (WIF1) in OPCs and showed exacerbated EAE progression in both the spinal cord and the brain. Genetic or antibody-mediated ablation of CC-chemokine ligand 4 (CCL4) prevented infiltration of CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells and arrested disease progression in these mice. A characterization of CNS (central nervous system) immune cell clusters identified an augmented subpopulation of NK1.1\n                    <jats:sup>+<\/jats:sup>\n                    CD11b\n                    <jats:sup>+<\/jats:sup>\n                    Gr-1\n                    <jats:sup>+<\/jats:sup>\n                    cytotoxic macrophages in\n                    <jats:italic>\n                      Pdgfra\n                      <jats:sup>CreER<\/jats:sup>\n                      ;Apc\n                      <jats:sup>fl\/fl<\/jats:sup>\n                    <\/jats:italic>\n                    EAE mice. Microinjection of this subpopulation of macrophages into the brains of wild-type C57\/B6J mice was sufficient to induce demyelination. Ablation of CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells prevented the effects of Wnt overactivation on demyelination and immune cell infiltration. Antagonizing chemokine receptor 5 (CCR5) using a European Medicines Agency\u2013approved drug, maraviroc, reduced immune cell infiltration, alleviated demyelination, and attenuated EAE progression. We found an OPC-orchestrated immune cellular network that instigates early demyelination, provides insight into MS pathophysiology, and suggests avenues for early interventions.\n                  <\/jats:p>","DOI":"10.1126\/scitranslmed.adn9980","type":"journal-article","created":{"date-parts":[[2025,4,2]],"date-time":"2025-04-02T16:32:02Z","timestamp":1743611522000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":29,"title":["Oligodendroglial precursor cells modulate immune response and early demyelination in a murine model of multiple sclerosis"],"prefix":"10.1126","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0397-6554","authenticated-orcid":true,"given":"Qi","family":"Wang","sequence":"first","affiliation":[{"name":"Research Centre, Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen 518107, China."},{"name":"Department of Histology and Embryology, Third Military Medical University, Chongqing 400038, China."},{"name":"Biomedical Analysis Center, Third Military Medical University, Chongqing 400038, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taida","family":"Huang","sequence":"additional","affiliation":[{"name":"Research Centre, Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen 518107, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1486-9586","authenticated-orcid":true,"given":"Zihan","family":"Zheng","sequence":"additional","affiliation":[{"name":"Biomedical Analysis Center, Third Military Medical University, Chongqing 400038, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8215-4270","authenticated-orcid":true,"given":"Yixun","family":"Su","sequence":"additional","affiliation":[{"name":"Research Centre, Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen 518107, China."},{"name":"Department of Histology and Embryology, Third Military Medical University, Chongqing 400038, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhonghao","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Histology and Embryology, Third Military Medical University, Chongqing 400038, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cong","family":"Zeng","sequence":"additional","affiliation":[{"name":"Biomedical Analysis Center, Third Military Medical University, Chongqing 400038, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guangdan","family":"Yu","sequence":"additional","affiliation":[{"name":"China Astronaut Research and Training Center, Beijing 100094, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Liu","sequence":"additional","affiliation":[{"name":"Biomedical Analysis Center, Third Military Medical University, Chongqing 400038, 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Third Military Medical University, Chongqing 400038, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinyu","family":"Zhang","sequence":"additional","affiliation":[{"name":"National Engineering Research Center of Immunological Products, Third Military Medical University, Chongqing 400038, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7825-0032","authenticated-orcid":true,"given":"Yuan","family":"Zhuang","sequence":"additional","affiliation":[{"name":"National Engineering Research Center of Immunological Products, Third Military Medical University, Chongqing 400038, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Tian","sequence":"additional","affiliation":[{"name":"Institute of Immunology, Third Military Medical University, Chongqing 400038, 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University of Traditional Chinese Medicine, Chengdu 610075, China."},{"name":"Department of Forensic Analytical Toxicology, School of Forensic Medicine, China Medical University, Shenyang 110122, China."},{"name":"Celica Biomedical, Technology Park 24, 1000 Ljubljana, Slovenia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7922-4434","authenticated-orcid":true,"given":"Ying","family":"Wan","sequence":"additional","affiliation":[{"name":"Biomedical Analysis Center, Third Military Medical University, Chongqing 400038, China."},{"name":"Institute for Translational Immunology, Chongqing 400038, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8686-4525","authenticated-orcid":true,"given":"Chenju","family":"Yi","sequence":"additional","affiliation":[{"name":"Research Centre, Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen 518107, China."},{"name":"Guangdong Provincial Key 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