{"doi":"10.1101/2022.12.15.520615","title":"Interleukin 31 receptor alpha induces airway hyperresponsiveness in asthma","abstract":"ABSTRACT Asthma is a chronic inflammatory airway disease characterized by airway hyperresponsiveness (AHR), inflammation, and goblet cell hyperplasia. Both Th1 and Th2 cytokines, including IFN-γ, IL-4, and IL-13 have been shown to induce asthma; however, the underlying mechanisms remain unclear. We observed a significant increase in the expression of IL-31RA, but not its cognate ligand IL-31 during house dust mite- and Schistosoma mansoni soluble egg antigen-induced allergic asthma. In support of this, IFN-γ and Th2 cytokines, IL-4 and IL-13, upregulated IL-31RA but not IL-31 in airway smooth muscle cells (ASMC). Importantly, the loss of IL-31RA attenuated AHR but had no effects on inflammation and goblet cell hyperplasia in allergic asthma or mice treated with IL-13 or IFNγ. Mechanistically, we demonstrate that IL-31RA functions as a positive regulator of muscarinic acetylcholine receptor 3 (CHRM3) expression and calcium signaling involved in the contractility of ASMC. Together, these results identified a novel role for IL-31RA in ASMC contractility and AHR distinct from airway inflammation and goblet cell hyperplasia in asthma. Summary The study identified an important role for the IL-31RA-CHRM3 axis in inducing airway hyperresponsiveness with limited changes in inflammation in allergic asthma. IL-31RA, whose expression is regulated by both Th1 and Th2 cytokines, augments the CHRM3-dependent contractility of ASMC and AHR.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2022,"id":314101,"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":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9587,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":587516,"name":"Dan JK Yombo","orcid":null,"position":1,"is_corresponding":false},{"id":1012710,"name":"Sanjana Yerubandi","orcid":"0000-0002-6383-6206","position":2,"is_corresponding":false},{"id":1013031,"name":"Bhanuprakash Reddy Geereddy","orcid":null,"position":3,"is_corresponding":false},{"id":458876,"name":"Francis X. McCormack","orcid":"0000-0001-7168-9464","position":4,"is_corresponding":false},{"id":416432,"name":"Satish K. Madala","orcid":"0000-0002-6042-5321","position":5,"is_corresponding":false},{"id":1013030,"name":"Santoshi Akkenepally","orcid":null,"position":0,"is_corresponding":true}],"reference_count":74,"raw_metadata":null,"created_at":"2026-07-19T00:33:48.490749Z","pmid":null,"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":[]}