{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T03:46:43Z","timestamp":1783396003213,"version":"3.54.6"},"reference-count":52,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2023,1,10]],"date-time":"2023-01-10T00:00:00Z","timestamp":1673308800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01DC013588"],"award-info":[{"award-number":["R01DC013588"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Int Forum Allergy Rhinol"],"published-print":{"date-parts":[[2023,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>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\u201025, 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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In this study, we used scRNAseq analysis, live cell imaging of intracellular calcium from primary sinonasal air\u2010liquid interface (ALI) cultures from 1 donor, and\u00a0measure 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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>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\u2010mediated signaling in response to succinate stimulation. Furthermore, we present evidence that primary sinonasal ALI cultures treated with succinate had increased levels of apical beta\u2010defensin 2, an antimicrobial peptide, compared to treatment with a control solution.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Overall, these findings demonstrate the need for further investigation into the activation of the sinonasal epithelium by succinate in the pathogenesis of CRS.<\/jats:p><\/jats:sec>","DOI":"10.1002\/alr.23104","type":"journal-article","created":{"date-parts":[[2022,12,24]],"date-time":"2022-12-24T17:07:55Z","timestamp":1671901675000},"page":"1525-1534","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Microbial metabolite succinate activates solitary chemosensory cells in the human sinonasal epithelium"],"prefix":"10.1002","volume":"13","author":[{"given":"Elizabeth A.","family":"Sell","sequence":"first","affiliation":[{"name":"Perelman School of Medicine, University of Pennsylvania  Philadelphia PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li Hui","family":"Tan","sequence":"additional","affiliation":[{"name":"Division of Rhinology Department of Otorhinolaryngology\u2010Head and Neck Surgery Perelman School of Medicine University of Pennsylvania  Philadelphia PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cailu","family":"Lin","sequence":"additional","affiliation":[{"name":"Monell Chemical Senses Center  Philadelphia PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John V.","family":"Bosso","sequence":"additional","affiliation":[{"name":"Division of Rhinology Department of Otorhinolaryngology\u2010Head and Neck Surgery Perelman School of Medicine University of Pennsylvania  Philadelphia PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James N.","family":"Palmer","sequence":"additional","affiliation":[{"name":"Division of Rhinology Department of Otorhinolaryngology\u2010Head and Neck Surgery Perelman School of Medicine University of Pennsylvania  Philadelphia PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nithin D.","family":"Adappa","sequence":"additional","affiliation":[{"name":"Division of Rhinology Department of Otorhinolaryngology\u2010Head and Neck Surgery Perelman School of Medicine University of Pennsylvania  Philadelphia PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert J.","family":"Lee","sequence":"additional","affiliation":[{"name":"Division of Rhinology Department of Otorhinolaryngology\u2010Head and Neck Surgery Perelman School of Medicine University of Pennsylvania  Philadelphia PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael A.","family":"Kohanski","sequence":"additional","affiliation":[{"name":"Division of Rhinology Department of Otorhinolaryngology\u2010Head and Neck Surgery Perelman School of Medicine University of Pennsylvania  Philadelphia PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danielle R.","family":"Reed","sequence":"additional","affiliation":[{"name":"Monell Chemical Senses Center  Philadelphia PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noam A.","family":"Cohen","sequence":"additional","affiliation":[{"name":"Perelman School of Medicine, University of Pennsylvania  Philadelphia PA"},{"name":"Division of Rhinology Department of Otorhinolaryngology\u2010Head and Neck Surgery Perelman School of Medicine University of Pennsylvania  Philadelphia PA"},{"name":"Monell Chemical Senses Center  Philadelphia PA"},{"name":"Corporal Michael J. 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