{"doi":"10.1101/2022.12.05.519197","title":"IL-6 prevents Th2 cell polarization by promoting SOCS3-dependent suppression of IL-2 signaling","abstract":"Abstract Defective interleukin-6 (IL-6) signaling has been associated with Th2 bias and elevated IgE. However, the underlying mechanism by which IL-6 prevents the development of Th2-driven diseases remains unknown. Using a model of house-dust-mite (HDM)-induced Th2 differentiation and allergic airway inflammation, we show that IL-6 signaling in allergen-specific T cells was required to prevent Th2 development and subsequent IgE response and allergic inflammation. Th2 cell lineage commitment required strong sustained IL-2 signaling. Importantly, we found that IL-6 turned off IL-2 signaling during early T cell activation and thus inhibited Th2 priming. Mechanistically, we found that IL-6-driven inhibition of IL-2 signaling in responding T cells was mediated by upregulation of Suppressor Of Cytokine Signaling 3 (SOCS3). This mechanism could be mimicked by pharmacological Janus Kinase-1 (JAK1) inhibition. Collectively, our results identify an unrecognized mechanism that prevents the development of unwanted Th2 cell responses and associated diseases and outline potential preventive interventions.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2022,"id":305078,"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":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9565,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":998988,"name":"Erin McLaughlin","orcid":null,"position":1,"is_corresponding":false},{"id":704143,"name":"Crystal Lewis","orcid":null,"position":2,"is_corresponding":false},{"id":703347,"name":"Amber M. Papillion","orcid":"0000-0001-9227-8314","position":3,"is_corresponding":false},{"id":479703,"name":"Etty Benveniste","orcid":"0000-0003-4120-5750","position":4,"is_corresponding":false},{"id":998989,"name":"Dave D. Hill","orcid":null,"position":5,"is_corresponding":false},{"id":293771,"name":"Alexander F. Rosenberg","orcid":null,"position":6,"is_corresponding":false},{"id":472049,"name":"André Ballesteros‐Tato","orcid":"0000-0002-4833-593X","position":7,"is_corresponding":false},{"id":623629,"name":"Beatriz León","orcid":"0000-0002-3793-3854","position":8,"is_corresponding":false},{"id":703346,"name":"Holly Bachus","orcid":"0000-0003-4368-1734","position":0,"is_corresponding":true}],"reference_count":55,"raw_metadata":null,"created_at":"2026-07-19T00:32:37.185846Z","pmid":null,"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":[]}