{"doi":"10.1016/j.celrep.2021.108955","title":"The anti-inflammatory cytokine interleukin-37 is an inhibitor of trained immunity","abstract":"Trained immunity (TI) is a de facto innate immune memory program induced in monocytes/macrophages by exposure to pathogens or vaccines, which evolved as protection against infections. TI is characterized by immunometabolic changes and histone post-translational modifications, which enhance production of pro-inflammatory cytokines. As aberrant activation of TI is implicated in inflammatory diseases, tight regulation is critical; however, the mechanisms responsible for this modulation remain elusive. Interleukin-37 (IL-37) is an anti-inflammatory cytokine that curbs inflammation and modulates metabolic pathways. In this study, we show that administration of recombinant IL-37 abrogates the protective effects of TI in vivo, as revealed by reduced host pro-inflammatory responses and survival to disseminated candidiasis. Mechanistically, IL-37 reverses the immunometabolic changes and histone post-translational modifications characteristic of TI in monocytes, thus suppressing cytokine production in response to infection. IL-37 thereby emerges as an inhibitor of TI and as a potential therapeutic target in immune-mediated pathologies.","journal":"Cell Reports","year":2021,"id":152885,"datarank":0.6435689161722588,"base_score":4.290459441148391,"endowment":4.290459441148391,"self_citation_contribution":0.6435689161722588,"citation_network_contribution":0.0,"self_endowment_contribution":0.6435689161722588,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":72,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9551,"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":235542,"name":"Isak W. Tengesdal","orcid":"0000-0002-8037-0428","position":1,"is_corresponding":false},{"id":245918,"name":"Mark S. Gresnigt","orcid":"0000-0002-9514-4634","position":2,"is_corresponding":false},{"id":110269,"name":"Travis Nemkov","orcid":"0000-0001-8566-7119","position":3,"is_corresponding":false},{"id":648638,"name":"Rob J.W. Arts","orcid":"0000-0002-6649-7190","position":4,"is_corresponding":false},{"id":104378,"name":"Jorge Domínguez‐Andrés","orcid":"0000-0002-9091-1961","position":5,"is_corresponding":false},{"id":648639,"name":"Raffaella Molteni","orcid":"0000-0002-5481-7572","position":6,"is_corresponding":false},{"id":110267,"name":"Davide Stefanoni","orcid":"0000-0002-7756-6788","position":7,"is_corresponding":false},{"id":648640,"name":"Eleonora Cantoni","orcid":"0000-0001-6502-4992","position":8,"is_corresponding":false},{"id":648641,"name":"Laura Cassina","orcid":"0000-0002-7350-3069","position":9,"is_corresponding":false},{"id":85852,"name":"María Rescigno","orcid":"0000-0002-6464-509X","position":10,"is_corresponding":false},{"id":235543,"name":"Kiki Schraa","orcid":"0000-0001-7265-1492","position":11,"is_corresponding":false},{"id":623883,"name":"Taylor Mills","orcid":"0000-0003-0030-4242","position":12,"is_corresponding":false},{"id":254785,"name":"Eric M. Pietras","orcid":"0000-0002-7339-8828","position":13,"is_corresponding":false},{"id":649171,"name":"Elan Z. Eisenmensser","orcid":null,"position":14,"is_corresponding":false},{"id":648642,"name":"Lorenzo Dagna","orcid":"0000-0002-7428-315X","position":15,"is_corresponding":false},{"id":648643,"name":"Alessandra Boletta","orcid":"0000-0002-4704-4006","position":16,"is_corresponding":false},{"id":28360,"name":"Angelo D’Alessandro","orcid":"0000-0002-2258-6490","position":17,"is_corresponding":false},{"id":104383,"name":"Leo A. B. Joosten","orcid":"0000-0001-6166-9830","position":18,"is_corresponding":false},{"id":104377,"name":"Mihai G. Netea","orcid":"0000-0003-2421-6052","position":19,"is_corresponding":false},{"id":235545,"name":"Charles A. Dinarello","orcid":"0000-0002-5073-8316","position":20,"is_corresponding":false},{"id":569754,"name":"Giulio Cavalli","orcid":"0000-0001-8728-3004","position":0,"is_corresponding":true}],"reference_count":49,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-18T23:43:34.972031Z","pmid":"33826894","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":[]}