{"doi":"10.1111/all.16402","title":"Endogenous Glucagon‐Like Peptide‐1 Receptor and Glucose‐Dependent Insulinotropic Polypeptide Receptor Signaling Inhibits Aeroallergen‐Induced Innate Airway Inflammation","abstract":"BACKGROUND: Anti-inflammatory effects of incretin signaling through the glucagon-like peptide-1 receptor (GLP-1R) and the glucose-dependent insulinotropic polypeptide receptor (GIPR) in mice have been reported. Therefore, we hypothesized that signaling through the endogenous GLP-1R and the GIPR individually decreases allergic airway inflammation and that the combination of GLP-1R and GIPR signaling together additively inhibits allergen-induced lung and airway inflammation. METHODS: WT (C57BL/6J), GLP-1R knockout (KO), GIPR KO, and GLP-1R/GIPR double KO (DKO) mice were challenged intranasally with Alternaria alternata extract (Alt-Ext) or vehicle to evaluate the impact of signaling through these receptors on the innate allergen-induced inflammatory response that is primarily driven by group 2 innate lymphoid cells (ILC2). RESULTS: Alt-Ext-induced IL-33 release in the bronchoalveolar lavage fluid (BALF) was not different between the mouse strains, but thymic stromal lymphopoietin (TSLP) was significantly increased in GLP-1R/GIPR DKO mice challenged with Alt-Ext compared to the other strains. Furthermore, Alt-Ext-induced protein expression of IL-5, IL-13, CCL11, and CCL24 in the lung homogenates, the number of eosinophils, lymphocytes, and neutrophils in the BALF, and the number of lung GATA3+ ILC2 were significantly increased in GLP-1R/GIPR DKO mice compared to the other 3 strains. Furthermore, ICAM-1 expression on lung epithelial cells was increased in GLP-1R/GIPR DKO mice challenged with Alt-Ext compared to the other 3 strains. CONCLUSIONS: Deficiency of both GLP-1R and GIPR signaling together increased TSLP release, ILC2 activation, and early type 2 innate immune responses to aeroallergen exposure. Combined GLP-1R and GIPR signaling should be explored for the treatment of asthma.","journal":"Allergy","year":2024,"id":455042,"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":7,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9568,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1192963,"name":"Masako Abney","orcid":null,"position":1,"is_corresponding":false},{"id":1059310,"name":"Jian Zhang","orcid":"0000-0001-5552-0132","position":2,"is_corresponding":false},{"id":1059907,"name":"Mark Rusznak","orcid":null,"position":3,"is_corresponding":false},{"id":518362,"name":"Christian M. Warren","orcid":null,"position":4,"is_corresponding":false},{"id":289419,"name":"Dawn C. Newcomb","orcid":"0000-0003-2592-9433","position":5,"is_corresponding":false},{"id":263307,"name":"Katherine N. Cahill","orcid":"0000-0002-8549-1835","position":6,"is_corresponding":false},{"id":237001,"name":"Daniel J. Drucker","orcid":"0000-0001-6688-8127","position":7,"is_corresponding":false},{"id":264402,"name":"Kevin D. Niswender","orcid":"0000-0001-6994-8738","position":8,"is_corresponding":false},{"id":290007,"name":"R. Stokes Peebles","orcid":"0000-0002-1429-7875","position":9,"is_corresponding":false},{"id":715523,"name":"Shinji Toki","orcid":"0000-0003-4379-9118","position":0,"is_corresponding":true}],"reference_count":48,"raw_metadata":null,"created_at":"2026-07-19T02:03:17.458329Z","pmid":"39559998","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":[]}