{"doi":"10.1093/immhor/vlaf043","title":"Genetic deletion of <i>Alx/Fpr2</i> differentially regulates pulmonary inflammation in the absence and presence of acute lung injury","abstract":"The inflammation resolution receptor lipoxin A4/formyl peptide receptor 2 (ALX/FPR2) plays a critical role in immune regulation by binding select oxylipins derived from n-6 and n-3 polyunsaturated fatty acids (PUFAs). While ALX/FPR2 is implicated in controlling inflammation initiation and resolution, its specific role in pulmonary inflammatory responses remains unclear. In this study, we investigated how genetic deletion of Alx/Fpr2 controls oxylipin levels, immune cell populations, and inflammatory cytokines under conditions of homeostasis and injury. Alx/Fpr2 knockout (KO) mice exhibited normal food intake and weight gain but showed impaired glucose and lipid metabolism. Targeted lipidomic analyses by liquid chromatography-tandem mass spectrometry revealed elevated pulmonary concentrations of n-6 and n-3 PUFA-derived oxylipins in KO mice compared to controls. Flow cytometry further demonstrated increased lung infiltration of NK cells, monocytes, and lymphoid cells, indicating a proinflammatory state in the absence of injury. Following 24 h of LPS-induced acute lung injury, IL-1β levels were elevated in KO mice, but pulmonary histopathology, immune cell numbers, and oxylipin levels were comparable to those of controls. These results suggested a protective role of ALX/FPR2 upon acute lung injury, which led us to further investigate the role of ALX/FPR2 upon 72 h of lung injury. Indeed, Alx/Fpr2 KO mice showed reduced bronchoalveolar lavage protein concentration and lower levels of IL-6 and TNF-α. Collectively, these findings demonstrate that ALX/FPR2 deficiency promotes basal pulmonary inflammation but protects against prolonged injury-induced inflammation, highlighting the context-dependent role of this receptor in pulmonary inflammation.","journal":"ImmunoHorizons","year":2025,"id":524458,"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":4,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9544,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":884090,"name":"Madeline Behee","orcid":null,"position":1,"is_corresponding":false},{"id":345494,"name":"Abrar E. Al‐Shaer","orcid":"0000-0001-7836-6844","position":2,"is_corresponding":false},{"id":1398514,"name":"Megan Wagner","orcid":null,"position":3,"is_corresponding":false},{"id":506770,"name":"Michael Armstrong","orcid":"0000-0002-6062-6318","position":4,"is_corresponding":false},{"id":254385,"name":"Nichole Reisdorph","orcid":"0000-0002-0425-8012","position":5,"is_corresponding":false},{"id":1237183,"name":"Brooke E Bathon","orcid":null,"position":6,"is_corresponding":false},{"id":1237184,"name":"Nari Beatty","orcid":null,"position":7,"is_corresponding":false},{"id":346627,"name":"Traci Davis","orcid":null,"position":8,"is_corresponding":false},{"id":655293,"name":"Michael J. Yaeger","orcid":"0000-0001-7039-6360","position":9,"is_corresponding":false},{"id":178835,"name":"Rosemary S. Gray","orcid":null,"position":10,"is_corresponding":false},{"id":1237182,"name":"Meagan D Bridges","orcid":null,"position":11,"is_corresponding":false},{"id":305236,"name":"Kymberly M. Gowdy","orcid":"0000-0002-7227-0697","position":12,"is_corresponding":false},{"id":284926,"name":"Saame Raza Shaikh","orcid":"0000-0003-1950-2521","position":13,"is_corresponding":false},{"id":908315,"name":"Rafia Virk","orcid":"0000-0002-1729-6616","position":0,"is_corresponding":true}],"reference_count":85,"raw_metadata":null,"created_at":"2026-07-19T02:50:12.083054Z","pmid":"40972651","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":[]}