{"doi":"10.1152/ajplung.00204.2020","title":"Therapeutic efficacy of IL-17A neutralization with corticosteroid treatment in a model of antigen-driven mixed-granulocytic asthma","abstract":"Many mouse models of allergic asthma exhibit eosinophil-predominant cellularity rather than the mixed-granulocytic cytology in steroid-unresponsive severe disease. Therefore, we sought to implement a novel mouse model of antigen-driven, mixed-granulocytic, severe allergic asthma to determine biomarkers of the disease process and potential therapeutic targets. C57BL/6J wild-type, interleukin-6 knockout (IL-6−/−), and IL-6 receptor knockout (IL-6R−/−), mice were injected with an emulsion of complete Freund’s adjuvant and house dust mite antigen (CFA/HDM) on day 1. Dexamethasone, a lymphocyte-depleting biological, or anti-IL-17A was administered during the intranasal HDM challenge on days 19–22. On day 23, the CFA/HDM model elicited mixed bronchoalveolar lavage (BAL) cellularity (typically 80% neutrophils and 10% eosinophils), airway hyperresponsiveness (AHR) to methacholine, diffusion impairment, lung damage, body weight loss, corticosteroid resistance, and elevated levels of serum amyloid A (SAA), pro-inflammatory cytokines, and T helper type 1/ T helper type 17 (Th1/Th17) cytokines compared with eosinophilic models of HDM-driven allergic airway disease. BAL cells in IL-6- or IL-6R-deficient mice were predominantly eosinophilic and associated with elevated T helper type 2 (Th2) and reduced Th1/Th17 cytokine production, along with an absence of SAA. Nevertheless, AHR remained in IL-6-deficient mice even when dexamethasone was administered. However, combined administration of anti-IL-17A and systemic corticosteroid significantly attenuated both overall and neutrophilic airway inflammation and also reduced AHR and body weight loss. Inhibition of IL-17A combined with systemic corticosteroid treatment during antigen-driven exacerbations may provide a novel therapeutic approach to prevent the pathological pulmonary and constitutional changes that greatly impact patients with the mixed-granulocytic endotype of severe asthma.","journal":"American Journal of Physiology-Lung Cellular and Molecular Physiology","year":2020,"id":105645,"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":23,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9397,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":511235,"name":"Madeleine M. Mank","orcid":"0000-0002-0617-4736","position":1,"is_corresponding":false},{"id":511685,"name":"Leah F. Reed","orcid":null,"position":2,"is_corresponding":false},{"id":511236,"name":"Camille Walton","orcid":"0000-0001-9166-5419","position":3,"is_corresponding":false},{"id":511686,"name":"Katherine E. Van Der Vliet","orcid":null,"position":4,"is_corresponding":false},{"id":511237,"name":"Jennifer L. Ather","orcid":"0000-0003-0484-5599","position":5,"is_corresponding":false},{"id":511238,"name":"David G. Chapman","orcid":"0000-0002-8211-1817","position":6,"is_corresponding":false},{"id":424000,"name":"Bradford J. Smith","orcid":"0000-0002-1583-6762","position":7,"is_corresponding":false},{"id":259970,"name":"Mercedes Rincón","orcid":"0000-0002-6663-2225","position":8,"is_corresponding":false},{"id":336717,"name":"Matthew E. Poynter","orcid":"0000-0002-7578-4570","position":9,"is_corresponding":false},{"id":511234,"name":"Katherine Menson","orcid":"0000-0002-3673-7210","position":0,"is_corresponding":true}],"reference_count":72,"raw_metadata":null,"created_at":"2026-07-18T23:12:21.275494Z","pmid":"32783616","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":[]}