{"doi":"10.1172/jci.insight.143366","title":"A role for IL-33–activated ILC2s in eosinophilic vasculitis","abstract":"Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare but serious disease with poorly understood mechanisms. Here, we report that patients with EGPA have elevated levels of TSLP, IL-25, and soluble ST2, which are well-characterized cytokine \"alarmins\" that activate or modulate type 2 innate lymphoid cells (ILC2s). Patients with active EGPA have a concurrent reduction in circulating ILC2s, suggesting a role for ILC2s in the pathogenesis of this disease. To explore the mechanism of these findings in patients, we established a model of EGPA in which active vasculitis and pulmonary hemorrhage were induced by IL-33 administration in predisposed, hypereosinophilic mice. In this model, induction of pulmonary hemorrhage and vasculitis was dependent on ILC2s and signaling through IL4Rα. In the absence of IL4Rα or STAT6, IL-33-treated mice had less vascular leak and pulmonary edema, less endothelial activation, and reduced eotaxin production, cumulatively leading to a reduction of pathologic eosinophil migration into the lung parenchyma. These results offer a mouse model for use in future mechanistic studies of EGPA, and they suggest that IL-33, ILC2s, and IL4Rα signaling may be potential targets for further study and therapeutic targeting in patients with EGPA.","journal":"JCI Insight","year":2021,"id":160460,"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":35,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9438,"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":673595,"name":"Jérémie Dion","orcid":"0000-0002-1135-0351","position":1,"is_corresponding":false},{"id":478432,"name":"Steven J. Van Dyken","orcid":"0000-0002-9787-0883","position":2,"is_corresponding":false},{"id":80220,"name":"Roberto R. Ricardo-Gonzalez","orcid":"0000-0002-6135-4035","position":3,"is_corresponding":false},{"id":674497,"name":"Claire Danel","orcid":null,"position":4,"is_corresponding":false},{"id":673596,"name":"Camille Taillé","orcid":"0000-0001-9768-5728","position":5,"is_corresponding":false},{"id":673597,"name":"Luc Mouthon","orcid":"0000-0002-7021-9492","position":6,"is_corresponding":false},{"id":80235,"name":"Richard M. Locksley","orcid":"0000-0002-5468-6867","position":7,"is_corresponding":false},{"id":104179,"name":"Benjamin Terrier","orcid":"0000-0001-6612-7336","position":8,"is_corresponding":false},{"id":673594,"name":"Maya E. Kotas","orcid":"0000-0002-8102-6346","position":0,"is_corresponding":true}],"reference_count":48,"raw_metadata":null,"created_at":"2026-07-18T23:44:48.240577Z","pmid":"33974563","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":[]}