{"doi":"10.1101/2023.03.16.533006","title":"Autophagy functions in lung macrophages and dendritic cells to regulate allergen-dependent inflammatory responses","abstract":"ABSTRACT Asthma affects 260 million people worldwide, with severe asthma cases that are associated with T H 17/T H 1 responses and neutrophil dominated inflammation being the most difficult to treat due to corticosteroid insensitivity. Single nucleotide polymorphisms in the ATG5 gene, which encodes for a protein required for the cellular recycling process of autophagy, are associated with higher risk for developing severe asthma. However, the role for ATG5 during allergic inflammation remains mostly unknown. We have identified an autophagy-dependent role for ATG5 in lung macrophages and dendritic cells (DCs) for suppressing T H 17 responses and neutrophil accumulation in house dust mite (HDM)-challenged mice, a T H 17/T H 1 dominated model for allergic airway inflammation due to contamination of the HDM with lipopolysaccharide. In contrast, autophagy was required to promote eosinophil accumulation in the T H 2-dominated ovalbumin model of allergic airway inflammation, supporting a model where autophagy functions in lung macrophages and DCs to suppress T H 17 responses and promote T H 2 responses in an allergen-dependent manner. In addition, we discover that autophagy is also required in macrophages exposed to HDM to suppress the secretion of cytokines and chemokines that would otherwise recruit neutrophils to the lungs, independent of T cell responses. Together, our data identify multiple roles for autophagy in suppressing the neutrophil accumulation in lungs that is associated with severe asthma.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2023,"id":396042,"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":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9557,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":991545,"name":"Reilly Woodson","orcid":null,"position":1,"is_corresponding":false},{"id":889647,"name":"Skyler V. Hendrix","orcid":"0000-0002-0644-6519","position":2,"is_corresponding":false},{"id":506977,"name":"Anne Rosén","orcid":"0000-0002-7656-3382","position":3,"is_corresponding":false},{"id":986714,"name":"Rachel L. Kinsella","orcid":"0009-0003-4191-5047","position":4,"is_corresponding":false},{"id":991117,"name":"Samuel R. McKee","orcid":"0009-0005-7166-2153","position":5,"is_corresponding":false},{"id":1025923,"name":"Marick Starick","orcid":"0000-0003-4227-7852","position":6,"is_corresponding":false},{"id":593272,"name":"Christina L. Stallings","orcid":"0000-0002-2747-5618","position":7,"is_corresponding":false},{"id":889648,"name":"Sumanta Kumar Naik","orcid":"0000-0003-4499-0811","position":8,"is_corresponding":false},{"id":917727,"name":"Asya Smirnov","orcid":"0000-0003-4767-1680","position":9,"is_corresponding":false},{"id":987160,"name":"Darren Kreamalmeyer","orcid":null,"position":10,"is_corresponding":false},{"id":19797,"name":"Andrew L. Kau","orcid":"0000-0002-9386-3766","position":11,"is_corresponding":false},{"id":991118,"name":"Neha Dubey","orcid":"0009-0005-1581-9099","position":0,"is_corresponding":true}],"reference_count":130,"raw_metadata":null,"created_at":"2026-07-19T01:19:27.044553Z","pmid":"40799574","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":[]}