{"doi":"10.4049/jimmunol.2300884","title":"IL-10 Differentially Promotes Mast Cell Responsiveness to IL-33, Resulting in Enhancement of Type 2 Inflammation and Suppression of Neutrophilia","abstract":"Mast cells (MCs) play critical roles in the establishment of allergic diseases. We recently demonstrated an unexpected, proinflammatory role for IL-10 in regulating MC responses. IL-10 enhanced MC activation and promoted IgE-dependent responses during food allergy. However, whether these effects extend to IgE-independent stimuli is not clear. In this article, we demonstrate that IL-10 plays a critical role in driving IL-33-mediated MC responses. IL-10 stimulation enhanced MC expansion and degranulation, ST2 expression, IL-13 production, and phospho-relA upregulation in IL-33-treated cells while suppressing TNF-α. These effects were partly dependent on endogenous IL-10 and further amplified in MCs coactivated with both IL-33 and IgE/Ag. IL-10's divergent effects also extended in vivo. In a MC-dependent model of IL-33-induced neutrophilia, IL-10 treatment enhanced MC responsiveness, leading to suppression of neutrophils and decreased TNF-α. In contrast, during IL-33-induced type 2 inflammation, IL-10 priming exacerbated MC activity, resulting in MC recruitment to various tissues, enhanced ST2 expression, induction of hypothermia, recruitment of eosinophils, and increased MCPT-1 and IL-13 levels. Our data elucidate an important role for IL-10 as an augmenter of IL-33-mediated MC responses, with implications during both allergic diseases and other MC-dependent disorders. IL-10 induction is routinely used as a prognostic marker of disease improvement. Our data suggest instead that IL-10 can enhance ST2 responsiveness in IL-33-activated MCs, with the potential to both aggravate or suppress disease severity depending on the inflammatory context.","journal":"The Journal of Immunology","year":2024,"id":463794,"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":5,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.957,"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":412603,"name":"Dylan Krajewski","orcid":null,"position":1,"is_corresponding":false},{"id":1294152,"name":"Chelsea Garcia","orcid":"0000-0002-7681-695X","position":2,"is_corresponding":false},{"id":1294535,"name":"Caitlin Tedeschi","orcid":null,"position":3,"is_corresponding":false},{"id":411432,"name":"Stephanie Polukort","orcid":"0009-0004-3323-2374","position":4,"is_corresponding":false},{"id":412605,"name":"Jeffrey Rovatti","orcid":null,"position":5,"is_corresponding":false},{"id":693816,"name":"Mohamed Mire","orcid":"0000-0003-2468-5289","position":6,"is_corresponding":false},{"id":1294153,"name":"Christopher N. Blesso","orcid":"0000-0002-4434-4839","position":7,"is_corresponding":false},{"id":305930,"name":"Evan R. Jellison","orcid":"0009-0004-2674-1605","position":8,"is_corresponding":false},{"id":333509,"name":"Sallie S. Schneider","orcid":"0000-0003-0093-4308","position":9,"is_corresponding":false},{"id":384854,"name":"John Ryan","orcid":"0000-0002-9203-5512","position":10,"is_corresponding":false},{"id":411434,"name":"Clinton B. Mathias","orcid":"0000-0002-0223-4842","position":11,"is_corresponding":false},{"id":1172280,"name":"Saurav Ranjitkar","orcid":null,"position":0,"is_corresponding":true}],"reference_count":94,"raw_metadata":null,"created_at":"2026-07-19T02:04:33.257852Z","pmid":"38497670","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":[]}