{"doi":"10.1111/all.70122","title":"Prolonged <scp>IL</scp> ‐33 Exposure Switches the Secreted Mast Cell Cytokine Profile From Pro‐Inflammatory to Pro‐Tolerant","abstract":"BACKGROUND: During desensitization, the immune response to an allergen switches from a type 2 inflammation towards immunological tolerance. Subcutaneous Hymenoptera venom and alum injections induce IL-33 release during venom immunotherapy (VIT). To elucidate whether mast cells (MCs) contribute to this switch in immune response, we investigated the effect of IL-33 and Hymenoptera venom on MC cytokine profiles under VIT-like conditions. METHODS: LAD2 cells or primary human skin MCs were stimulated with IL-33 and Hymenoptera venom or Compound 48/80, with or without IL-33 pre-exposure (priming) for up to four days. In addition, c-kit was stimulated or inhibited. Cell surface marker expression was monitored by flow cytometry. Secreted cytokines were measured in supernatants by a bead-based multiplex assay and ELISA. Phosphorylated c-kit was determined by Western blot. RESULTS: LAD2 cell stimulation led to the secretion of IL-2, IL-5, IL-6, IL-13, TNF-α, and TGF-β1, phosphorylation of c-kit, and a reduced c-kit surface expression after 24 h. IL-33 primed LAD2 cells secreted mainly the tolerance-promoting cytokine TGF-β1 but little pro-inflammatory/type 2 cytokines, showed less c-kit phosphorylation, and a higher c-kit surface expression following stimulation. Inhibition of c-kit before stimulation led to a similar secreted cytokine profile phenotype as IL-33 priming. IL-33 primed skin MCs showed a comparable cytokine switch and receptor expression pattern. CONCLUSION: Changes in the interaction of IL-33 receptor (ST2) and c-kit after prolonged IL-33 exposure skewed MCs towards tolerance-promoting cytokines during desensitization therapy. These findings suggest a trendsetting role of MCs for the type of response towards Hymenoptera venom.","journal":"Allergy","year":2025,"id":527253,"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":0.9549,"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":1391454,"name":"Carolin Költgen","orcid":null,"position":1,"is_corresponding":false},{"id":77605,"name":"Magda Babina","orcid":"0000-0002-4500-7615","position":2,"is_corresponding":false},{"id":949153,"name":"Peter Wolf","orcid":"0000-0001-7777-9444","position":3,"is_corresponding":false},{"id":1328441,"name":"Andrea Teufelberger","orcid":"0000-0002-1142-949X","position":0,"is_corresponding":true}],"reference_count":50,"raw_metadata":null,"created_at":"2026-07-19T02:50:39.280101Z","pmid":"41117102","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":[]}