{"doi":"10.1111/all.15072","title":"IL‐37 regulates allergic inflammation by counterbalancing pro‐inflammatory IL‐1 and IL‐33","abstract":"BACKGROUND: Children with asthma have impaired production of interleukin (IL) 37; in mice, IL-37 reduces hallmarks of experimental allergic asthma (EAA). However, it remains unclear how IL-37 exerts its inhibitory properties in asthma. This study aimed to identify the mechanism(s) by which IL-37 controls allergic inflammation. METHODS: IL-37 target cells were identified by single-cell RNA-seq of IL-1R5 and IL-1R8. Airway tissues were isolated by laser-capture microdissection and examined by microarray-based gene expression analysis. Mononuclear cells (MNC) and airway epithelial cells (AECs) were isolated and stimulated with allergen, IL-1β, or IL-33 together with recombinant human (rh) IL-37. Wild-type, IL-1R1- and IL-33-deficient mice with EAA were treated with rhIL-37. IL-1β, IL-33, and IL-37 levels were determined in sputum and nasal secretions from adult asthma patients without glucocorticoid therapy. RESULTS: IL-37 target cells included AECs, T cells, and dendritic cells. In mice with EAA, rhIL-37 led to differential expression of >90 genes induced by IL-1β and IL-33. rhIL-37 reduced production of Th2 cytokines in allergen-activated MNCs from wild-type but not from IL-1R1-deficient mice and inhibited IL-33-induced Th2 cytokine release. Furthermore, rhIL-37 attenuated IL-1β- and IL-33-induced pro-inflammatory mediator expression in murine AEC cultures. In contrast to wild-type mice, hIL-37 had no effect on EAA in IL-1R1- or IL-33-deficient mice. We also observed that expression/production ratios of both IL-1β and IL-33 to IL-37 were dramatically increased in asthma patients compared to healthy controls. CONCLUSION: IL-37 downregulates allergic airway inflammation by counterbalancing the disease-amplifying effects of IL-1β and IL-33.","journal":"Allergy","year":2021,"id":157730,"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":49,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9555,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":665112,"name":"Lars Lunding","orcid":"0000-0002-5278-3129","position":1,"is_corresponding":false},{"id":40339,"name":"Ulrich M. Zissler","orcid":"0000-0003-4826-3419","position":2,"is_corresponding":false},{"id":665113,"name":"Christina Vock","orcid":"0000-0003-3936-3426","position":3,"is_corresponding":false},{"id":665700,"name":"Sina Webering","orcid":null,"position":4,"is_corresponding":false},{"id":665701,"name":"Johanna C. Ehlers","orcid":null,"position":5,"is_corresponding":false},{"id":665114,"name":"Zane Orinska","orcid":"0000-0003-0834-5321","position":6,"is_corresponding":false},{"id":40340,"name":"Adam Chaker","orcid":"0000-0002-5117-4073","position":7,"is_corresponding":false},{"id":1253,"name":"Carsten B. Schmidt‐Weber","orcid":"0000-0002-3203-8084","position":8,"is_corresponding":false},{"id":4816,"name":"Niklas J. Lang","orcid":"0000-0002-7452-8292","position":9,"is_corresponding":false},{"id":573,"name":"Herbert B. Schiller","orcid":"0000-0001-9498-7034","position":10,"is_corresponding":false},{"id":277383,"name":"Marcus Mall","orcid":"0000-0002-4057-2199","position":11,"is_corresponding":false},{"id":665115,"name":"Heinz Fehrenbach","orcid":"0000-0003-1935-9411","position":12,"is_corresponding":false},{"id":235545,"name":"Charles A. Dinarello","orcid":"0000-0002-5073-8316","position":13,"is_corresponding":false},{"id":665116,"name":"Michael Wegmann","orcid":"0000-0002-1658-1554","position":14,"is_corresponding":false},{"id":665699,"name":"Alexandra Schröder","orcid":null,"position":0,"is_corresponding":true}],"reference_count":93,"raw_metadata":null,"created_at":"2026-07-18T23:44:21.786014Z","pmid":"34460953","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":[]}