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We hypothesized that Fc<jats:sub>\u03b3<\/jats:sub>RIIb activation by deposited IgG could inhibit tissue damage during I\/R. Our results showed that I\/R induction led to the deposition of IgG in intestinal tissue during the reperfusion phase. Death upon I\/R occurred earlier and was more frequent in Fc<jats:sub>\u03b3<\/jats:sub>RIIb<jats:sup>\u2212\/\u2212<\/jats:sup> than WT mice. The higher lethality rate was associated with greater tissue injury and bacterial translocation to other organs. Fc<jats:sub>\u03b3<\/jats:sub>RIIb<jats:sup>\u2212\/\u2212<\/jats:sup> mice presented changes in the amount and repertoire of circulating IgG, leading to increased IgG deposition in intestinal tissue upon reperfusion in these mice. Depletion of intestinal microbiota prevented antibody deposition and tissue damage in Fc<jats:sub>\u03b3<\/jats:sub>RIIb<jats:sup>\u2212\/\u2212<\/jats:sup> mice submitted to I\/R. We also observed increased production of ROS on neutrophils harvested from the intestines of Fc<jats:sub>\u03b3<\/jats:sub>RIIb<jats:sup>\u2212\/\u2212<\/jats:sup> mice submitted to I\/R. In contrast, Fc<jats:sub>\u03b3<\/jats:sub>RIII<jats:sup>\u2212\/\u2212<\/jats:sup> mice presented reduced tissue damage and neutrophil influx after reperfusion injury, a phenotype reversed by Fc<jats:sub>\u03b3<\/jats:sub>RIIb blockade. In addition, we observed reduced IFN\u2010\u03b2 expression in the intestines of Fc<jats:sub>\u03b3<\/jats:sub>RIII<jats:sup>\u2212\/\u2212<\/jats:sup> mice after I\/R, a phenotype that was also reverted by blocking Fc<jats:sub>\u03b3<\/jats:sub>RIIb. IFNAR<jats:sup>\u2212\/\u2212<\/jats:sup> mice submitted to I\/R presented reduced lethality and TNF release. Altogether our results demonstrate that antibody deposition triggers Fc<jats:sub>\u03b3<\/jats:sub>RIIb to control IFN\u2010\u03b2 and IFNAR activation and subsequent TNF release, tailoring tissue damage, and death induced by reperfusion injury.<\/jats:p>","DOI":"10.1111\/imm.13547","type":"journal-article","created":{"date-parts":[[2022,7,14]],"date-time":"2022-07-14T02:51:05Z","timestamp":1657767065000},"page":"428-442","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Fc<sub>\u03b3<\/sub>RIIb protects from reperfusion injury by controlling antibody and type I <scp>IFN<\/scp>\u2010mediated tissue injury and death"],"prefix":"10.1111","volume":"167","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4571-7238","authenticated-orcid":false,"given":"Camila Bernardo","family":"de Brito","sequence":"first","affiliation":[{"name":"Laborat\u00f3rio de Intera\u00e7\u00e3o Microrganismo\u2010Hospedeiro, Departamento de 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