biostudies-literatureDore ENatural Sciences and Engineering Research Council of Canadae152638https://www.ebi.ac.uk/biostudies/studies/S-EPMC8855825biostudies-literatureUnknown7(2)Secreted phospholipase A2-IIA (sPLA2-IIA) hydrolyzes phospholipids to liberate lysophospholipids and fatty acids. Given its poor activity toward eukaryotic cell membranes, its role in the generation of proinflammatory lipid mediators is unclear. Conversely, sPLA2-IIA efficiently hydrolyzes bacterial membranes. Here, we show that sPLA2-IIA affects the immune system by acting on the intestinal microbial flora. Using mice overexpressing transgene-driven human sPLA2-IIA, we found that the intestinal microbiota was critical for both induction of an immune phenotype and promotion of inflammatory arthritis. The expression of sPLA2-IIA led to alterations of the intestinal microbiota composition, but housing in a more stringent pathogen-free facility revealed that its expression could affect the imJCI insightThe interaction of secreted phospholipase A2-IIA with the microbiota alters its lipidome and promotes inflammation.PMC8855825RGPIN-2016-05830Rangachari MDavidovic LCloutier NBoilard EMorozumi SAllaeys IDuchez ACPayre CArita MMartin CJoly-Beauparlant CFlamand NDroit ABodein APetit-Paitel ALevesque TLambeau GGelb MHMurakami MDore EMathieu ALeclercq MfalseThe interaction of secreted phospholipase A2-IIA with the microbiota alters its lipidome and promotes inflammation.Secreted phospholipase A2-IIA (sPLA2-IIA) hydrolyzes phospholipids to liberate lysophospholipids and fatty acids. Given its poor activity toward eukaryotic cell membranes, its role in the generation of proinflammatory lipid mediators is unclear. Conversely, sPLA2-IIA efficiently hydrolyzes bacterial membranes. Here, we show that sPLA2-IIA affects the immune system by acting on the intestinal microbial flora. Using mice overexpressing transgene-driven human sPLA2-IIA, we found that the intestinal microbiota was critical for both induction of an immune phenotype and promotion of inflammatory arthritis. The expression of sPLA2-IIA led to alterations of the intestinal microbiota composition, but housing in a more stringent pathogen-free facility revealed that its expression could affect the im2022-01-01T00:00:00Z2022 Jan2026-05-30T23:54:54.471Z2025-04-04T23:29:06.051ZS-EPMC88558253507602710.1172/jci.insight.152638