{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T05:06:16Z","timestamp":1784696776334,"version":"3.55.0"},"reference-count":72,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T00:00:00Z","timestamp":1784678400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>\n                    Resolution of inflammation is an active process that requires efferocytosis, the engulfment of apoptotic cells by macrophages, mediated by receptors such as MerTK. IL-33 is an alarmin that initiates type 2 immune responses, including increased production of IL-13, which promotes MerTK expression. The ability of IL-33 to promote efferocytosis\n                    <jats:italic>in vivo<\/jats:italic>\n                    was examined. Intraperitoneal administration of IL-33 to mice increased local MerTK\n                    <jats:sup>+<\/jats:sup>\n                    macrophage numbers within 48h. MerTK\n                    <jats:sup>+<\/jats:sup>\n                    macrophages were not similarly induced by free mitochondria, an alternative cell damage associated signal. Efferocytotic activity was increased rapidly in response to apoptotic thymocytes in IL-33-treated mice. The established inducer of MerTK expression, IL-13, was detected in peritoneal lavage fluid shortly after IL-33 administration. Peritoneal eosinophils expressed the IL-33 receptor and demonstrated both intracellular IL-13 by flow cytometry and significantly increased\n                    <jats:italic>Il13<\/jats:italic>\n                    transcript expression following IL-33 treatment. In contrast, neither elevated IL-13 expression nor IL-13 protein secretion was observed in peritoneal lymphocyte populations within the first 6 hours after IL-33 administration. Primary cultures of bone marrow-derived mouse mast cells and eosinophils demonstrated IL-13 protein responses to IL-33 administration within 6\u00a0h. Mast cell-deficient Cpa3-Cre; Mcl-1\n                    <jats:sup>fl\/fl<\/jats:sup>\n                    mice had significantly reduced IL-13 levels in the peritoneal cavity 3 hours after IL-33 administration when compared with mast cell-containing littermates. In contrast, IL-33-treated eosinophil-deficient \u0394dblGATA mice had similar levels of IL-13 at this time point as wild type controls. These data demonstrate that IL-33 promotes MerTK expression, critical for efferocytosis by macrophages, by a process associated with an early rapid local increase in IL-13 production to which mast cells are a substantial early contributor. These findings contribute to our understanding of clinical situations where elevated soluble IL-33 receptor (sST2) and\/or lower mast cell numbers are associated with worse clinical outcome.\n                  <\/jats:p>","DOI":"10.3389\/fimmu.2026.1802300","type":"journal-article","created":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T04:42:00Z","timestamp":1784695320000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["IL-33 promotes efferocytosis by peritoneal macrophages by a mechanism associated with rapid granulocyte IL-13 production"],"prefix":"10.3389","volume":"17","author":[{"given":"Stephanie A.","family":"Legere","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, Dalhousie University","place":["Halifax, NS, Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roopa Hebbandi","family":"Nanjundappa","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Dalhousie University","place":["Halifax, NS, Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dihia","family":"Meghnem","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Dalhousie University","place":["Halifax, NS, Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian D.","family":"Haidl","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Dalhousie University","place":["Halifax, NS, Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Edgar","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Dalhousie University","place":["Halifax, NS, 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