{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T09:46:05Z","timestamp":1774950365565,"version":"3.50.1"},"reference-count":40,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2026,3,29]],"date-time":"2026-03-29T00:00:00Z","timestamp":1774742400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100015326","name":"National Institutes of Health (NIH)\n              https:\/\/ror.org\/01cwqze88","doi-asserted-by":"publisher","award":["R01HL076179"],"award-info":[{"award-number":["R01HL076179"]}],"id":[{"id":"10.13039\/100015326","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100015326","name":"National Institutes of Health (NIH)\n              https:\/\/ror.org\/01cwqze88","doi-asserted-by":"publisher","award":["R35GM118337"],"award-info":[{"award-number":["R35GM118337"]}],"id":[{"id":"10.13039\/100015326","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Gut ischemia\/reperfusion (I\/R) injury releases damage-associated molecular patterns (DAMPs), such as extracellular cold-inducible RNA-binding protein (eCIRP). Milk fat globule\u2013epidermal growth factor VIII-derived oligopeptide 3 (MOP3) is a novel peptide enabling macrophage uptake of eCIRP via \u03b1v\u03b23-integrin. MOP3 reduces inflammation in gut I\/R, but its mechanisms are not completely understood. We hypothesized MOP3 promotes macrophage polarization toward an anti-inflammatory, M2-like phenotype in gut I\/R. We induced gut I\/R in mice through 60 min of superior mesenteric artery occlusion followed by 4 h of reperfusion. Intestines were evaluated for macrophage polarization by flow cytometry and immunofluorescence histology. Peritoneal cavity macrophages were isolated from mice and treated with eCIRP, MOP3, \u03b1v\u03b23-antibody, and\/or na\u00efve IgG for 4 or 24 h. Polarity was assessed by flow cytometry, qPCR, and ELISA. Compared to the sham, the M2 proportion after gut I\/R decreased by 22.7%, and the M1 proportion increased by 241%. MOP3 treatment increased the M2 proportion by 64.3%, and the M1 proportion decreased by 22.7%. In eCIRP-stimulated macrophages, MOP3 treatment increased M2-like and reduced M1-like cell-surface markers, gene expression, and cytokine levels. \u03b1v\u03b23 antibody dramatically reduced MOP3\u2032s effects. MOP3 promotes M2 polarization through \u03b1v\u03b23 integrin-mediated clearance of eCIRP, a novel mechanism whereby MOP3 reduces gut I\/R injury.<\/jats:p>","DOI":"10.3390\/cells15070606","type":"journal-article","created":{"date-parts":[[2026,3,30]],"date-time":"2026-03-30T13:41:03Z","timestamp":1774878063000},"page":"606","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["MFG-E8-Derived Oligopeptide MOP3 Facilitates Anti-Inflammatory M2-like Macrophage Polarization in Gut Ischemia\/Reperfusion"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0143-3337","authenticated-orcid":false,"given":"Russell","family":"Hollis","sequence":"first","affiliation":[{"name":"Center for Immunology and Inflammation, The Feinstein Institutes for Medical Research, Manhasset, NY 11030, USA"},{"name":"Department of Surgery, Zucker School of Medicine, Manhasset, NY 11030, USA"},{"name":"Elmezzi Graduate School of Molecular Medicine, Northwell Health, Manhasset, NY 11030, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuichi","family":"Akama","sequence":"additional","affiliation":[{"name":"Center for Immunology and Inflammation, The Feinstein Institutes for Medical Research, Manhasset, NY 11030, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yongchan","family":"Lee","sequence":"additional","affiliation":[{"name":"Center for Immunology and Inflammation, The Feinstein Institutes for Medical Research, Manhasset, NY 11030, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jingsong","family":"Li","sequence":"additional","affiliation":[{"name":"Center for Immunology and Inflammation, The Feinstein Institutes for Medical Research, Manhasset, NY 11030, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8620-0609","authenticated-orcid":false,"given":"Megan","family":"Tenet","sequence":"additional","affiliation":[{"name":"Center for Immunology and Inflammation, The Feinstein Institutes for Medical Research, Manhasset, NY 11030, USA"},{"name":"Department of Surgery, Zucker School of Medicine, Manhasset, NY 11030, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8195-4505","authenticated-orcid":false,"given":"Monowar","family":"Aziz","sequence":"additional","affiliation":[{"name":"Center for Immunology and Inflammation, The Feinstein Institutes for Medical Research, Manhasset, NY 11030, USA"},{"name":"Department of Surgery, Zucker School of Medicine, Manhasset, NY 11030, USA"},{"name":"Elmezzi Graduate School of Molecular Medicine, Northwell Health, Manhasset, NY 11030, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1557-0394","authenticated-orcid":false,"given":"Ping","family":"Wang","sequence":"additional","affiliation":[{"name":"Center for Immunology and Inflammation, The Feinstein Institutes for Medical Research, Manhasset, NY 11030, USA"},{"name":"Department of Surgery, Zucker School of Medicine, Manhasset, NY 11030, USA"},{"name":"Elmezzi Graduate School of Molecular Medicine, Northwell Health, Manhasset, NY 11030, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Fitridge, R., and Thompson, M. 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