{"doi":"10.1016/j.celrep.2025.115294","title":"Lung CD4+ resident memory T cells use airway secretory cells to stimulate and regulate onset of allergic airway neutrophilic disease","abstract":"<h2>Summary</h2> Neutrophilic asthma is a vexing disease, but mechanistic and therapeutic advancements will require better models of allergy-induced airway neutrophilia. Here, we find that periodic ovalbumin (OVA) inhalation in sensitized mice elicits rapid allergic airway inflammation and pathophysiology mimicking neutrophilic asthma. OVA-experienced murine lungs harbor diverse clusters of CD4<sup>+</sup> resident memory T (T<sub>RM</sub>) cells, including unconventional RORγt<sup>negative/low</sup> T helper 17 (T<sub>H</sub>17) cells. Acute OVA challenge instigates interleukin (IL)-17A secretion from these T<sub>RM</sub> cells, driving CXCL5 production from Muc5ac<sup>high</sup> airway secretory cells, leading to destructive airway neutrophilia. The T<sub>RM</sub> and epithelial cell signals discovered herein are also observed in adult human asthmatic airways. Epithelial antigen presentation regulates this biology by skewing T<sub>RM</sub> cells toward T<sub>H</sub>2 and T<sub>H</sub>1 fates so that T<sub>H</sub>1-related interferon (IFN)-γ suppresses IL-17A-driven, CXCL5-mediated airway neutrophilia. Concordantly, <i>in vivo</i> IFN-γ supplementation improves disease outcomes. Thus, using our model of neutrophilic asthma, we identify lung epithelial-CD4<sup>+</sup> T<sub>RM</sub> cell crosstalk as a key rheostat of allergic airway neutrophilia.","journal":"Cell Reports","year":2025,"id":515698,"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":12,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9595,"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":630272,"name":"F.T. Korkmaz","orcid":"0000-0002-1158-7164","position":1,"is_corresponding":false},{"id":630269,"name":"C. Lyon De Ana","orcid":"0000-0002-2964-1624","position":2,"is_corresponding":false},{"id":378390,"name":"Lu Lu","orcid":"0000-0002-6174-3209","position":3,"is_corresponding":false},{"id":1381080,"name":"Feng-Zhi Shao","orcid":null,"position":4,"is_corresponding":false},{"id":790266,"name":"C. Odom","orcid":"0000-0002-1164-8481","position":5,"is_corresponding":false},{"id":630271,"name":"Kimberly A. Barker","orcid":"0000-0003-4612-9144","position":6,"is_corresponding":false},{"id":630273,"name":"Aditya Ramanujan","orcid":"0000-0003-2055-6826","position":7,"is_corresponding":false},{"id":1381081,"name":"E. Niszczak","orcid":null,"position":8,"is_corresponding":false},{"id":631393,"name":"Wesley N. Goltry","orcid":null,"position":9,"is_corresponding":false},{"id":422670,"name":"Ian Martin","orcid":"0000-0001-6934-8257","position":10,"is_corresponding":false},{"id":1245437,"name":"C. Ha","orcid":null,"position":11,"is_corresponding":false},{"id":422672,"name":"Lee J. Quinton","orcid":"0000-0003-1938-2507","position":12,"is_corresponding":false},{"id":422671,"name":"Matthew R. Jones","orcid":"0000-0003-4647-2962","position":13,"is_corresponding":false},{"id":1085689,"name":"Alan Fine","orcid":"0000-0001-9351-3048","position":14,"is_corresponding":false},{"id":29914,"name":"Joshua D. Welch","orcid":"0000-0002-5869-2391","position":15,"is_corresponding":false},{"id":625544,"name":"Felicia Chen","orcid":"0000-0001-6092-1774","position":16,"is_corresponding":false},{"id":110438,"name":"Anna C. Belkina","orcid":"0000-0001-7967-6254","position":17,"is_corresponding":false},{"id":89954,"name":"Joseph P. Mizgerd","orcid":"0000-0002-4042-3169","position":18,"is_corresponding":false},{"id":422668,"name":"Anukul T. Shenoy","orcid":"0000-0001-8861-2295","position":19,"is_corresponding":false},{"id":1380606,"name":"Vijay Raaj Ravi","orcid":"0000-0001-9489-1606","position":0,"is_corresponding":true}],"reference_count":117,"raw_metadata":null,"created_at":"2026-07-19T02:48:44.647022Z","pmid":"39965565","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":[]}