{"doi":"10.1111/imm.13766","title":"Pla2g5 contributes to viral‐like‐induced lung inflammation through macrophage proliferation and LA/Ffar1 lung cell recruitment","abstract":"Abstract Macrophages expressing group V phospholipase A 2 (Pla2g5) release the free fatty acid (FFA) linoleic acid (LA), potentiating lung type 2 inflammation. Although Pla2g5 and LA increase in viral infections, their role remains obscure. We generated Pla2g5 flox/flox mice, deleted Pla2g5 by using the Cx3cr1 cre transgene, and activated bone marrow‐derived macrophages (BM‐Macs) with poly:IC, a synthetic double‐stranded RNA that triggers a viral‐like immune response, known Pla2g5‐dependent stimuli (IL‐4, LPS + IFNγ, IL‐33 + IL‐4 + GM‐CSF) and poly:IC + LA followed by lipidomic and transcriptomic analysis. Poly:IC‐activated Pla2g5 flox/flox ; Cx3cr1 cre/+ BM‐Macs had downregulation of major bioactive lipids and critical enzymes producing those bioactive lipids. In addition, AKT phosphorylation was lower in poly:IC‐stimulated Pla2g5 flox/flox ; Cx3cr1 cre/+ BM‐Macs, which was not restored by adding LA to poly:IC‐stimulated BM‐Macs. Consistently, Pla2g5 flox/flox ; Cx3cr1 cre/+ mice had diminished poly:IC‐induced lung inflammation, including inflammatory macrophage proliferation, while challenging Pla2g5 flox/flox ; Cx3cr1 cre/+ mice with poly:IC + LA partially restored lung inflammation and inflammatory macrophage proliferation. Finally, mice lacking FFA receptor‐1 ( Ffar1 )‐null mice had reduced poly:IC‐induced lung cell recruitment and tissue macrophage proliferation, not corrected by LA. Thus, Pla2g5 contributes to poly:IC‐induced lung inflammation by regulating inflammatory macrophage proliferation and LA/Ffar1‐mediated lung cell recruitment and tissue macrophage proliferation.","journal":"Immunology","year":2024,"id":446405,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":6,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9543,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":104337,"name":"Daniel F. Dwyer","orcid":"0000-0001-5029-261X","position":1,"is_corresponding":false},{"id":303882,"name":"Kinan Alhallak","orcid":"0000-0002-0512-0357","position":2,"is_corresponding":false},{"id":1053954,"name":"Jun Nagai","orcid":"0000-0003-4720-5065","position":3,"is_corresponding":false},{"id":470339,"name":"Kendall Zaleski","orcid":null,"position":4,"is_corresponding":false},{"id":301606,"name":"Sachin K. Samuchiwal","orcid":"0000-0001-6232-5650","position":5,"is_corresponding":false},{"id":1053957,"name":"Hiroaki Hayashi","orcid":"0000-0002-8836-5068","position":6,"is_corresponding":false},{"id":1232925,"name":"Airi Nishida","orcid":null,"position":7,"is_corresponding":false},{"id":857568,"name":"Thomas I. Hirsch","orcid":"0000-0002-1373-2388","position":8,"is_corresponding":false},{"id":61589,"name":"Patrick J. Brennan","orcid":"0000-0003-0715-8209","position":9,"is_corresponding":false},{"id":354288,"name":"Mark Puder","orcid":"0000-0002-7941-2926","position":10,"is_corresponding":false},{"id":710018,"name":"Barbara Balestrieri","orcid":"0000-0002-0323-3278","position":11,"is_corresponding":false},{"id":1263680,"name":"Masaya Koganesawa","orcid":null,"position":0,"is_corresponding":true}],"reference_count":68,"raw_metadata":null,"created_at":"2026-07-19T02:01:50.465308Z","pmid":"38361249","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}