{"doi":"10.1093/jimmun/vkaf088","title":"PGI2 restricts trained ILC2 responses in allergic inflammation","abstract":"Pulmonary type 2 innate lymphoid cells (ILC2s) exhibit immune memory, termed \"trained immunity,\" which enhances their activation following exposure to an independent protease-containing allergen. The role of prostaglandin I2 (PGI2), a cyclooxygenase (COX) pathway metabolite, in modulating these trained ILC2 responses remains unclear. PGI2 acts through its G protein-coupled receptor IP. We hypothesized that IP signaling inhibits ILC2 training. To test this hypothesis, we used a mouse ILC2 training model in which we challenged wild-type (WT) and IP knockout (KO) mice with Alternaria alternata extract (Alt) to induce ILC2 activation and training. After a 33-d resting period, ILC2 responses subsided to a homeostatic level. Mice were then intranasally challenged with papain to evaluate responses to an unrelated allergen. IP KO mice displayed significantly heightened ILC2 interleukin (IL)-13 expression and with concomitant increased eosinophilia in the lungs post-papain challenge compared with WT control mice. Notably, neither WT nor IP KO mice challenged with papain only, devoid of ILC2 training, exhibited lung type 2 responses. The augmented type 2 inflammation observed in IP KO mice following both Alt and papain challenges correlated with increased numbers and percentages of IL-13-producing ILC2s and greater mean fluorescence intensity of IL-13 compared with WT mice. Furthermore, RNA sequencing of sorted ILC2s from WT and IP KO mice following Alt-papain challenges revealed heightened activation of immune response pathways and mitochondrial respiratory pathways in IP-deficient ILC2s. These findings reveal an inhibitory role of PGI2 signaling in trained ILC2 responses, emphasizing its pivotal contribution to innate immune responses and allergic inflammation.","journal":"The Journal of Immunology","year":2025,"id":525694,"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":3,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9547,"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":471688,"name":"Jian Zhang","orcid":"0000-0001-7217-0111","position":1,"is_corresponding":false},{"id":290002,"name":"Allison E. Norlander","orcid":"0000-0002-9357-485X","position":2,"is_corresponding":false},{"id":753628,"name":"Daniel P. Cook","orcid":"0000-0002-1152-4454","position":3,"is_corresponding":false},{"id":715523,"name":"Shinji Toki","orcid":"0000-0003-4379-9118","position":4,"is_corresponding":false},{"id":1192963,"name":"Masako Abney","orcid":null,"position":5,"is_corresponding":false},{"id":1059907,"name":"Mark Rusznak","orcid":null,"position":6,"is_corresponding":false},{"id":438867,"name":"Christopher Thomas","orcid":null,"position":7,"is_corresponding":false},{"id":518362,"name":"Christian M. Warren","orcid":null,"position":8,"is_corresponding":false},{"id":34720,"name":"Bradley W. Richmond","orcid":"0000-0001-6200-5235","position":9,"is_corresponding":false},{"id":456168,"name":"Katherine N. Gibson‐Corley","orcid":"0000-0002-1846-1580","position":10,"is_corresponding":false},{"id":297595,"name":"Ginger L. Milne","orcid":"0000-0003-3890-151X","position":11,"is_corresponding":false},{"id":289419,"name":"Dawn C. Newcomb","orcid":"0000-0003-2592-9433","position":12,"is_corresponding":false},{"id":290007,"name":"R. Stokes Peebles","orcid":"0000-0002-1429-7875","position":13,"is_corresponding":false},{"id":715524,"name":"Weisong Zhou","orcid":"0000-0002-4419-2302","position":0,"is_corresponding":true}],"reference_count":26,"raw_metadata":null,"created_at":"2026-07-19T02:50:25.860105Z","pmid":"40334085","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":[]}