{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T19:53:53Z","timestamp":1792785233635,"version":"4.5.0"},"reference-count":49,"publisher":"National Academy of Sciences","issue":"13","license":[{"start":{"date-parts":[[2025,3,25]],"date-time":"2025-03-25T00:00:00Z","timestamp":1742860800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000049","name":"HHS | NIH | National Institute on Aging","doi-asserted-by":"publisher","award":["RF1 AG051485"],"award-info":[{"award-number":["RF1 AG051485"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"HHS | NIH | National Institute on Aging","doi-asserted-by":"publisher","award":["P01 AG078106"],"award-info":[{"award-number":["P01 AG078106"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"HHS | NIH | National Institute on Aging","doi-asserted-by":"publisher","award":["R21 AG085133"],"award-info":[{"award-number":["R21 AG085133"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007625","name":"Cure Alzheimer's Fund","doi-asserted-by":"publisher","award":["no number"],"award-info":[{"award-number":["no number"]}],"id":[{"id":"10.13039\/100007625","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Fred and Ginger Haberle Charitable Fund at East Texas Communities Foundation","award":["no number"],"award-info":[{"award-number":["no number"]}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2025,4]]},"abstract":"<jats:p>\n                    We investigated the role of Triggering Receptor Expressed on Myeloid cells 2 (TREM2) in myelin regeneration in the brain. TREM2 is a receptor that activates microglia, which are crucial for clearing myelin debris and promoting remyelination. Previous studies in a mouse model of demyelination induced by the copper-chelating agent Cuprizone (CPZ) have shown that stimulation of TREM2 with a monoclonal antibody reduces demyelination, while deleting the\n                    <jats:italic>Trem2<\/jats:italic>\n                    gene in mice impairs remyelination. Here, we blocked TREM2 function acutely with an antibody during both the demyelination and remyelination phases of the CPZ model and analyzed the impact of the antibody treatment on myelination and gene expression in single cells. We found that blocking TREM2 depleted a distinct population of microglia with high expression of the transcription factor MAFB during remyelination. The loss of these MAFB-high microglia was linked to impaired generation of myelinating oligodendrocytes. Importantly, we identified MAFB\n                    <jats:sup>+<\/jats:sup>\n                    microglia in acute and acute-chronic brain lesions from individuals with multiple sclerosis (MS), but not in inactive lesions. We conclude that TREM2 is essential for maintaining a population of MAFB-high microglia that is associated with myelin repair. This finding has significant implications for understanding demyelinating diseases like MS and suggests that stimulating TREM2 could be a promising therapeutic approach for myelin repair.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2426786122","type":"journal-article","created":{"date-parts":[[2025,3,25]],"date-time":"2025-03-25T13:37:55Z","timestamp":1742909875000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":18,"title":["Acute TREM2 inhibition depletes MAFB-high microglia and hinders remyelination"],"prefix":"10.1073","volume":"122","author":[{"given":"Jinchao","family":"Hou","sequence":"first","affiliation":[{"name":"Department of Anesthesiology, Children\u2019s Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health","place":["Hangzhou, China"]},{"name":"Department of Pathology and Immunology, Washington University in St. Louis School of Medicine","place":["St. Louis"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberta","family":"Magliozzi","sequence":"additional","affiliation":[{"name":"Department of Brain Sciences, Faculty of Medicine, Imperial College London","place":["London, United Kingdom"]},{"name":"Neurology Section of Department of Neuroscience, Biomedicine and Movement, University of Verona","place":["Verona, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Pathology and Immunology, Washington University in St. Louis School of Medicine","place":["St. Louis"]},{"name":"Department of Neurology, Washington University School of Medicine","place":["St. Louis"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-2625-3230","authenticated-orcid":false,"given":"Junjie","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Pathology and Immunology, Washington University in St. Louis School of Medicine","place":["St. Louis"]},{"name":"Department of Mechanical Engineering and Materials Science, Washington University","place":["St. Louis"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"II","given":"John","family":"Wulf","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Washington University Center for Cellular Imaging, Washington University School of Medicine","place":["St. Louis"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregory","family":"Strout","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Washington University Center for Cellular Imaging, Washington University School of Medicine","place":["St. Louis"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2283-1863","authenticated-orcid":false,"given":"Xiangming","family":"Fang","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, The First Affiliated Hospital, Zhejiang University School of Medicine","place":["Hangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5222-4987","authenticated-orcid":false,"given":"Marco","family":"Colonna","sequence":"additional","affiliation":[{"name":"Department of Pathology and Immunology, Washington University in St. Louis School of Medicine","place":["St. Louis"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2025,3,25]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrn2480"},{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a041374"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1111\/nyas.14933"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1002\/glia.23229"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2010.04.002"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrn.2017.136"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1111\/imr.13416"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-023-00907-4"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-020-0654-2"},{"key":"e_1_3_4_10_2","doi-asserted-by":"crossref","first-page":"102877","DOI":"10.1016\/j.conb.2024.102877","article-title":"Microglia phagocytic mechanisms: Development informing disease","volume":"86","author":"Beiter R. M.","year":"2024","unstructured":"R. M. Beiter, P. W. Sheehan, D. P. Schafer, Microglia phagocytic mechanisms: Development informing disease. Curr. Opin. Neurobiol. 86, 102877 (2024).","journal-title":"Curr. Opin. Neurobiol."},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1111\/febs.16190"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2023.113574"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.33385"},{"key":"e_1_3_4_14_2","doi-asserted-by":"crossref","first-page":"6041","DOI":"10.1523\/JNEUROSCI.22-14-06041.2002","article-title":"Myelination is altered in insulin-like growth factor-I null mutant mice","volume":"22","author":"Ye P.","year":"2002","unstructured":"P. Ye, L. Li, R. G. Richards, R. P. DiAugustine, A. J. D\u2019Ercole, Myelination is altered in insulin-like growth factor-I null mutant mice. J. Neurosci. 22, 6041\u20136051 (2002).","journal-title":"J. Neurosci."},{"key":"e_1_3_4_15_2","first-page":"193","article-title":"Remyelination in experimental models of toxin-induced demyelination","volume":"318","author":"Blakemore W. F.","year":"2008","unstructured":"W. F. Blakemore, R. J. Franklin, Remyelination in experimental models of toxin-induced demyelination. Curr. Top. Microbiol. Immunol. 318, 193\u2013212 (2008).","journal-title":"Curr. Top. Microbiol. Immunol."},{"key":"e_1_3_4_16_2","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1186\/s13024-022-00538-8","article-title":"Oligodendrocyte death and myelin loss in the cuprizone model: An updated overview of the intrinsic and extrinsic causes of cuprizone demyelination","volume":"17","author":"Zirngibl M.","year":"2022","unstructured":"M. Zirngibl, P. Assinck, A. Sizov, A. V. Caprariello, J. R. Plemel, Oligodendrocyte death and myelin loss in the cuprizone model: An updated overview of the intrinsic and extrinsic causes of cuprizone demyelination. Mol. 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