FcγRIIb protects from reperfusion injury by controlling antibody and type I IFN-mediated tissue injury and death
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2022
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Intestinal ischemia and reperfusion (I/R) is accompanied by an exacerbated
inflammatory response characterized by deposition of IgG, release of inflammatory
mediators, and intense neutrophil influx in the small intestine, resulting in severe
tissue injury and death. We hypothesized that FcγRIIb 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 FcγRIIb / than WT mice.
The higher lethality rate was associated with greater tissue injury and bacterial
translocation to other organs. FcγRIIb / 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 FcγRIIb / mice submitted to I/R. We
also observed increased production of ROS on neutrophils harvested from the
intestines of FcγRIIb / mice submitted to I/R. In contrast, FcγRIII / mice pre sented reduced tissue damage and neutrophil influx after reperfusion injury, a phe notype reversed by FcγRIIb blockade. In addition, we observed reduced IFN-β
expression in the intestines of FcγRIII / mice after I/R, a phenotype that was also
reverted by blocking FcγRIIb. IFNAR / mice submitted to I/R presented reduced
lethality and TNF release. Altogether our results demonstrate that antibody deposi tion triggers FcγRIIb to control IFN-β and IFNAR activation and subsequent TNF
release, tailoring tissue damage, and death induced by reperfusion injury
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Autoantibodies, Gut, Inflammation, Microbiota, Neutrophil
Citação
BRITO, Camila Bernardo de et al. FcγRIIb protects from reperfusion injury by controlling antibody and typeI IFN-mediated tissue injury and death. Immunology, Oxford, v. 167, n. 3, p. 428-442, 2022. DOI: 10.1111/imm.13547. Disponível em: https://onlinelibrary.wiley.com/doi/10.1111/imm.13547. Acesso em: 19 mar. 2025.