{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,5]],"date-time":"2026-11-05T22:02:07Z","timestamp":1793916127581,"version":"4.8.0"},"reference-count":64,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"651","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Sci. Transl. Med."],"published-print":{"date-parts":[[2022,6,29]]},"abstract":"<jats:p>\n            The role of tissue-resident macrophages during tissue regeneration or fibrosis is not well understood, mainly due to the lack of a specific marker for their identification. Here, we identified three populations of skeletal muscle\u2013resident myelomonocytic cells: a population of macrophages positive for lymphatic vessel endothelial receptor 1 (LYVE1) and T cell membrane protein 4 (TIM4 or TIMD4), a population of LYVE1\n            <jats:sup>\u2212<\/jats:sup>\n            TIM4\n            <jats:sup>\u2212<\/jats:sup>\n            macrophages, and a population of cells likely representing dendritic cells that were positive for CD11C and major histocompatibility complex class II (MHCII). Using a combination of parabiosis and lineage-tracing experiments, we found that, at steady state, TIM4\n            <jats:sup>\u2212<\/jats:sup>\n            macrophages were replenished from the blood, whereas TIM4\n            <jats:sup>+<\/jats:sup>\n            macrophages locally self-renewed [self-renewing resident macrophages (SRRMs)]. We further showed that\n            <jats:italic>Timd4<\/jats:italic>\n            could be reliably used to distinguish SRRMs from damage-induced infiltrating macrophages. Using a colony-stimulating factor 1 receptor (CSF1R) inhibition\/withdrawal approach to specifically deplete SRRMs, we found that SRRMs provided a nonredundant function in clearing damage-induced apoptotic cells early after extensive acute injury. In contrast, in chronic mild injury as seen in a mouse model of Duchenne muscular dystrophy, depletion of both TIM4\n            <jats:sup>\u2212<\/jats:sup>\n            - and TIM4\n            <jats:sup>+<\/jats:sup>\n            -resident macrophage populations through long-term CSF1R inhibition changed muscle fiber composition from damage-sensitive glycolytic fibers toward damage-resistant glycolytic-oxidative fibers, thereby protecting muscle against contraction-induced injury both ex vivo and in vivo. This work reveals a previously unidentified role for resident macrophages in modulating tissue metabolism and may have therapeutic potential given the ongoing clinical testing of CSF1R inhibitors.\n          <\/jats:p>","DOI":"10.1126\/scitranslmed.abg7504","type":"journal-article","created":{"date-parts":[[2022,6,29]],"date-time":"2022-06-29T17:53:46Z","timestamp":1656525226000},"source":"Crossref","is-referenced-by-count":68,"title":["Metabolic reprogramming of skeletal muscle by resident macrophages points to CSF1R inhibitors as muscular dystrophy therapeutics"],"prefix":"10.1126","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6920-2450","authenticated-orcid":true,"given":"Farshad","family":"Babaeijandaghi","sequence":"first","affiliation":[{"name":"Biomedical Research Centre, University of British Columbia, Vancouver, BC V6T 1Z3, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0068-6471","authenticated-orcid":true,"given":"Ryan","family":"Cheng","sequence":"additional","affiliation":[{"name":"Biomedical Research Centre, University of British Columbia, Vancouver, BC V6T 1Z3, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nasim","family":"Kajabadi","sequence":"additional","affiliation":[{"name":"Biomedical Research Centre, University of British Columbia, Vancouver, BC V6T 1Z3, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hesham","family":"Soliman","sequence":"additional","affiliation":[{"name":"Biomedical Research Centre, University of British Columbia, Vancouver, BC V6T 1Z3, Canada."},{"name":"Department of Pharmacology and Toxicology, Faculty of Pharmacy, Minia University, Minia 61519, Egypt."},{"name":"Aspect Biosystems, 1781 W 75th Ave, Vancouver, BC V6P 6P2, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chih-Kai","family":"Chang","sequence":"additional","affiliation":[{"name":"Biomedical Research Centre, University of British Columbia, Vancouver, BC V6T 1Z3, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1873-0696","authenticated-orcid":true,"given":"Josh","family":"Smandych","sequence":"additional","affiliation":[{"name":"Biomedical Research Centre, University of British Columbia, Vancouver, BC V6T 1Z3, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin Wei","family":"Tung","sequence":"additional","affiliation":[{"name":"Biomedical Research Centre, University of British Columbia, Vancouver, BC V6T 1Z3, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7513-4028","authenticated-orcid":true,"given":"Reece","family":"Long","sequence":"additional","affiliation":[{"name":"Biomedical Research Centre, University of British Columbia, Vancouver, BC V6T 1Z3, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amirhossein","family":"Ghassemi","sequence":"additional","affiliation":[{"name":"Biomedical Research Centre, University of British Columbia, Vancouver, BC V6T 1Z3, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0368-2620","authenticated-orcid":true,"given":"Fabio M. 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