{"doi":"10.1172/jci187907","title":"Allergens abrogate antiinflammatory DNA effects and unmask macrophage-driven neutrophilic asthma via ILC2/STING/TNF-α signaling","abstract":"The mechanisms of neutrophilic and mixed neutrophilic-eosinophilic asthma are poorly understood. We found that extracellular DNA and nucleosomes (Nucs) were elevated in the airways of patients with neutrophilic-eosinophilic asthma and correlated with bronchoalveolar lavage neutrophils. Bronchial tissue from neutrophilic-eosinophilic asthma had more DNA sensor-positive cells. Intranasally administered DNA did not induce airway hyperreactivity (AHR) or any pathology but induced AHR and neutrophilic-eosinophilic inflammation when coadministered with the allergen Alternaria (Alt). Nuc alone induced antiinflammatory/defensive genes, whereas the Nuc-Alt combination increased levels of TNF-α and innate cytokines. The Alt-Nuc phenotype was abolished in Cgas-/-, ALR-/-, Sting-/-, LysMCre:Stingfl/fl, IL7RCre:Rorαfl/fl, and Tnfr2-/- mice. Alt, unexpectedly, played an essential role in the Nuc-induced phenotype. It abrogated Nuc induction of antiinflammatory genes, facilitated Nuc uptake, induced type 2 innate lymphoid cells, which, in the presence of Nuc, produced high levels of TNF-α, and promoted neutrophilic infiltration. We established a paradigm whereby allergens inhibit the antiinflammatory effects of DNA/Nuc and facilitate STING-TNF-α-driven neutrophilic-eosinophilic inflammation in asthma.","journal":"Journal of Clinical Investigation","year":2025,"id":526002,"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":0.9577,"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":647932,"name":"Divya Verma","orcid":"0000-0002-0746-6642","position":1,"is_corresponding":false},{"id":1401079,"name":"Rangati Varma","orcid":"0000-0003-1813-3285","position":2,"is_corresponding":false},{"id":329663,"name":"Kapil Sirohi","orcid":"0000-0001-5039-2848","position":3,"is_corresponding":false},{"id":1401521,"name":"Carolyn Kwiat","orcid":null,"position":4,"is_corresponding":false},{"id":1401522,"name":"Mohini Pathria","orcid":null,"position":5,"is_corresponding":false},{"id":329664,"name":"Mukesh Verma","orcid":"0000-0002-1817-0863","position":6,"is_corresponding":false},{"id":776050,"name":"Anita Sahu","orcid":"0000-0001-9552-922X","position":7,"is_corresponding":false},{"id":1401080,"name":"Vamsi P. Guntur","orcid":"0000-0002-3210-8265","position":8,"is_corresponding":false},{"id":445117,"name":"Laurie A. Manka","orcid":"0000-0003-4839-7812","position":9,"is_corresponding":false},{"id":303832,"name":"Brian Vestal","orcid":"0000-0002-3772-1691","position":10,"is_corresponding":false},{"id":407619,"name":"Camille M. Moore","orcid":"0000-0002-7363-8684","position":11,"is_corresponding":false},{"id":281779,"name":"Richard J. Martin","orcid":"0000-0003-2478-5239","position":12,"is_corresponding":false},{"id":329668,"name":"Magdalena M. Gorska","orcid":"0000-0001-7364-8703","position":13,"is_corresponding":false},{"id":411835,"name":"John C. Cambier","orcid":"0000-0002-7803-242X","position":14,"is_corresponding":false},{"id":411836,"name":"Andrew Getahun","orcid":"0000-0002-5663-6812","position":15,"is_corresponding":false},{"id":330485,"name":"Rafeul Alam","orcid":null,"position":16,"is_corresponding":false},{"id":329667,"name":"Anand Sripada","orcid":"0000-0002-5163-6637","position":0,"is_corresponding":true}],"reference_count":44,"raw_metadata":null,"created_at":"2026-07-19T02:50:25.860105Z","pmid":"40526428","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":[]}