{"doi":"10.1002/alr.23104","title":"Microbial metabolite succinate activates solitary chemosensory cells in the human sinonasal epithelium","abstract":"BACKGROUND: Succinate, although most famous for its role in the Krebs cycle, can be released extracellularly as a signal of cellular distress, particularly in situations of metabolic stress and inflammation. Solitary chemosensory cells (SCCs) express SUCNR1, the succinate receptor, and modulate type 2 inflammatory responses in helminth and protozoal infections in the small intestine. SCCs are the dominant epithelial source of interleukin-25, as well as an important source of cysteinyl leukotrienes in the airway, and have been implicated as upstream agents in type 2 inflammation in chronic rhinosinusitis (CRS) and asthma. METHODS: In this study, we used scRNAseq analysis, live cell imaging of intracellular calcium from primary sinonasal air-liquid interface (ALI) cultures from 1 donor, and measure antimicrobial peptide release from 5 donors to demonstrate preliminary evidence suggesting that succinate can act as a stimulant of SCCs in the human sinonasal epithelium. RESULTS: Results from scRNAseq analysis show that approximately 10% of the SCC/ionocyte cluster of cells expressed SUCNR1 as well as a small population of immune cells. Using live cell imaging of intracellular calcium, we also demonstrate that clusters of cells on primary sinonasal ALI cultures initiated calcium-mediated signaling in response to succinate stimulation. Furthermore, we present evidence that primary sinonasal ALI cultures treated with succinate had increased levels of apical beta-defensin 2, an antimicrobial peptide, compared to treatment with a control solution. CONCLUSION: Overall, these findings demonstrate the need for further investigation into the activation of the sinonasal epithelium by succinate in the pathogenesis of CRS.","journal":"International Forum of Allergy & Rhinology","year":2022,"id":265590,"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":11,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9589,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"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":432281,"name":"Li Tan","orcid":"0000-0003-4352-654X","position":1,"is_corresponding":false},{"id":247554,"name":"Cailu Lin","orcid":"0000-0001-8909-7758","position":2,"is_corresponding":false},{"id":433222,"name":"John V. Bosso","orcid":null,"position":3,"is_corresponding":false},{"id":232128,"name":"Nithin D. Adappa","orcid":"0000-0002-7535-9339","position":4,"is_corresponding":false},{"id":579445,"name":"Robert J. Lee","orcid":"0000-0001-5826-6686","position":6,"is_corresponding":false},{"id":264133,"name":"Michael A. Kohanski","orcid":"0000-0001-8399-364X","position":7,"is_corresponding":false},{"id":247555,"name":"Danielle R. Reed","orcid":"0000-0002-4374-6107","position":8,"is_corresponding":false},{"id":264137,"name":"Noam A. Cohen","orcid":"0000-0002-9462-3932","position":9,"is_corresponding":false},{"id":6573,"name":"Elizabeth Sell","orcid":"0000-0002-9658-1107","position":0,"is_corresponding":true}],"reference_count":53,"raw_metadata":null,"created_at":"2026-07-19T00:26:49.862989Z","pmid":"36565436","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":[]}