{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T15:02:43Z","timestamp":1785855763844,"version":"3.56.0"},"reference-count":51,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2025,11,1]],"date-time":"2025-11-01T00:00:00Z","timestamp":1761955200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100002850","name":"Fondo Nacional de Desarrollo Cient\u00edfico y Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["1221257"],"award-info":[{"award-number":["1221257"]}],"id":[{"id":"10.13039\/501100002850","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002850","name":"Fondo Nacional de Desarrollo Cient\u00edfico y Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["220118"],"award-info":[{"award-number":["220118"]}],"id":[{"id":"10.13039\/501100002850","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002850","name":"Fondo Nacional de Desarrollo Cient\u00edfico y Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["FONDECYT Postdoctoral 3220672"],"award-info":[{"award-number":["FONDECYT Postdoctoral 3220672"]}],"id":[{"id":"10.13039\/501100002850","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000292","name":"Cystic Fibrosis Trust","doi-asserted-by":"publisher","award":["SRC013"],"award-info":[{"award-number":["SRC013"]}],"id":[{"id":"10.13039\/501100000292","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000292","name":"Cystic Fibrosis Trust","doi-asserted-by":"publisher","award":["1211838"],"award-info":[{"award-number":["1211838"]}],"id":[{"id":"10.13039\/501100000292","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100001003","name":"Boehringer Ingelheim","doi-asserted-by":"publisher","award":["DC000566"],"award-info":[{"award-number":["DC000566"]}],"id":[{"id":"10.13039\/100001003","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Vicerrector\u00eda de Investigaci\u00f3n y Doctorados de la Universidad San Sebasti\u00e1n","award":["USS-FIN-23-FAPE-14"],"award-info":[{"award-number":["USS-FIN-23-FAPE-14"]}]},{"name":"Vicerrector\u00eda de Investigaci\u00f3n y Doctorados de la Universidad San Sebasti\u00e1n","award":["TARRAN22G0"],"award-info":[{"award-number":["TARRAN22G0"]}]},{"DOI":"10.13039\/501100002850","name":"Fondo Nacional de Desarrollo Cient\u00edfico y Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["1221257"],"award-info":[{"award-number":["1221257"]}],"id":[{"id":"10.13039\/501100002850","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002850","name":"Fondo Nacional de Desarrollo Cient\u00edfico y Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["220118"],"award-info":[{"award-number":["220118"]}],"id":[{"id":"10.13039\/501100002850","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002850","name":"Fondo Nacional de Desarrollo Cient\u00edfico y Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["FONDECYT Postdoctoral 3220672"],"award-info":[{"award-number":["FONDECYT Postdoctoral 3220672"]}],"id":[{"id":"10.13039\/501100002850","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002850","name":"Cystic Fibrosis Trust","doi-asserted-by":"publisher","award":["SRC013"],"award-info":[{"award-number":["SRC013"]}],"id":[{"id":"10.13039\/501100002850","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002850","name":"Cystic Fibrosis Trust","doi-asserted-by":"publisher","award":["1211838"],"award-info":[{"award-number":["1211838"]}],"id":[{"id":"10.13039\/501100002850","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002850","name":"Boehringer Ingelheim","doi-asserted-by":"publisher","award":["DC000566"],"award-info":[{"award-number":["DC000566"]}],"id":[{"id":"10.13039\/501100002850","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Vicerrector\u00eda de Investigaci\u00f3n y Doctorados de la Universidad San Sebasti\u00e1n","award":["USS-FIN-23-FAPE-14"],"award-info":[{"award-number":["USS-FIN-23-FAPE-14"]}]},{"name":"Vicerrector\u00eda de Investigaci\u00f3n y Doctorados de la Universidad San Sebasti\u00e1n","award":["TARRAN22G0"],"award-info":[{"award-number":["TARRAN22G0"]}]}],"content-domain":{"domain":["www.atsjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2025,11,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The respiratory tract possesses a highly regulated innate defense system that includes cilia-mediated mucociliary clearance (MCC). Efficient MCC relies on appropriate hydration of airway surfaces, which is controlled by a blend of transepithelial sodium and liquid absorption, as well as anion and liquid secretion. The latter is mediated primarily by the cystic fibrosis transmembrane conductance regulator (CFTR) anion channel. Succinate is derived from parasites, microorganisms, and inflammatory cells, and its concentration increases in the airway surface liquid during infections, activating the G protein\u2013coupled succinate receptor (SUCNR1), which acts as a succinate sensor. Because MCC is tightly regulated by second messengers, we tested the hypothesis that succinate signaling was linked to CFTR activity. We observed that SUCNR1 activation stimulated anion secretion, increased mucus transport, and induced tracheal constriction in mouse airways. In the Cftr\u0394F508\/\u0394F508 mouse, increased mucus transport and tracheal constriction were not observed, whereas succinate-induced electrogenic anion secretion remained unaffected. Stimulation of normal human bronchial epithelial cells with succinate activated CFTR-dependent anion secretion and increased airway surface liquid height. Moreover, human bronchial epithelial cells derived from \u0394F508-CF individuals that lacked succinate-induced anion secretion, unless incubated with elexacaftor-tezacaftor-ivacaftor, which restored succinate-induced anion secretion, confirmed the tight relationship between SUCNR1 signaling and CFTR function. We have identified a novel mechanism for regulating CFTR\/MCC activation that is defective in cystic fibrosis airways. We propose that succinate acts as a danger molecule that alerts the airways to the presence of pathogens leading to a flushing out of the airways.<\/jats:p>","DOI":"10.1165\/rcmb.2024-0225oc","type":"journal-article","created":{"date-parts":[[2025,4,16]],"date-time":"2025-04-16T14:43:21Z","timestamp":1744814601000},"page":"769-779","update-policy":"https:\/\/doi.org\/10.1164\/crossmarkpolicies","source":"Crossref","is-referenced-by-count":3,"title":["Succinate Chemosensing Induces Cystic Fibrosis Transmembrane Conductance Regulator-dependent Airway Clearance that Is Impaired in Cystic Fibrosis"],"prefix":"10.1093","volume":"73","author":[{"given":"T\u00e1bata","family":"Apablaza","sequence":"first","affiliation":[{"name":"Centro de Estudios Cient\u00edficos, Valdivia, Chile"},{"name":"Facultad de Medicina and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marisol","family":"Barros-Poblete","sequence":"additional","affiliation":[{"name":"Centro de Estudios Cient\u00edficos, Valdivia, Chile"},{"name":"Universidad Austral de Chile, Valdivia, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Livia","family":"Delpiano","sequence":"additional","affiliation":[{"name":"Biosciences Institute, The Medical School, Newcastle University, Newcastle upon Tyne, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra","family":"Villanueva","sequence":"additional","affiliation":[{"name":"Centro de Estudios Cient\u00edficos, Valdivia, Chile"},{"name":"Facultad de Medicina and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anita","family":"Guequen","sequence":"additional","affiliation":[{"name":"Centro de Estudios Cient\u00edficos, Valdivia, Chile"},{"name":"Universidad Austral de Chile, Valdivia, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B\u00e1rbara","family":"Tapia-Balladares","sequence":"additional","affiliation":[{"name":"Centro de Estudios Cient\u00edficos, Valdivia, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iram","family":"Haq","sequence":"additional","affiliation":[{"name":"Translational and Clinical Research Institute, The Medical School, Newcastle University, Newcastle upon Tyne, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Felipe","family":"Tribi\u00f1os","sequence":"additional","affiliation":[{"name":"Universidad Austral de Chile, Valdivia, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebasti\u00e1n","family":"Hern\u00e1ndez-Rivas","sequence":"additional","affiliation":[{"name":"Centro de Estudios Cient\u00edficos, Valdivia, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernard","family":"Verdon","sequence":"additional","affiliation":[{"name":"Biosciences Institute, The Medical School, Newcastle University, Newcastle upon Tyne, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew G. S.","family":"Biggart","sequence":"additional","affiliation":[{"name":"Division of Genetic, Environmental and Inhalational Disease, Department of Internal Medicine, Kansas University Medical Center, Kansas City, Kansas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yenniffer","family":"S\u00e1nchez","sequence":"additional","affiliation":[{"name":"Centro de Estudios Cient\u00edficos, Valdivia, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6954-9611","authenticated-orcid":false,"given":"Christopher","family":"Ward","sequence":"additional","affiliation":[{"name":"Translational and Clinical Research Institute, The Medical School, Newcastle University, Newcastle upon Tyne, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B. Dnate\u2019","family":"Baxter","sequence":"additional","affiliation":[{"name":"Department of Cell and Developmental Biology, University of Colorado Anschutz Medical Campus, Aurora, Colorado; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diego","family":"Restrepo","sequence":"additional","affiliation":[{"name":"Department of Cell and Developmental Biology, University of Colorado Anschutz Medical Campus, Aurora, Colorado; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabel","family":"Cornejo","sequence":"additional","affiliation":[{"name":"Centro de Estudios Cient\u00edficos, Valdivia, Chile"},{"name":"Facultad de Ciencias para el Cuidado de la Salud, Universidad San Sebasti\u00e1n, Valdivia, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8598-2642","authenticated-orcid":false,"given":"Robert","family":"Tarran","sequence":"additional","affiliation":[{"name":"Division of Genetic, Environmental and Inhalational Disease, Department of Internal Medicine, Kansas University Medical Center, Kansas City, Kansas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcelo A.","family":"Catal\u00e1n","sequence":"additional","affiliation":[{"name":"Instituto de Fisiolog\u00eda, Universidad Austral de Chile, Valdivia, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael A.","family":"Gray","sequence":"additional","affiliation":[{"name":"Biosciences Institute, The Medical School, Newcastle University, Newcastle upon Tyne, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3813-1909","authenticated-orcid":false,"given":"Carlos A.","family":"Flores","sequence":"additional","affiliation":[{"name":"Centro de Estudios Cient\u00edficos, Valdivia, Chile"},{"name":"Facultad de Medicina and"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,11,1]]},"reference":[{"key":"2026012204144277500_bib1","doi-asserted-by":"crossref","first-page":"1809","DOI":"10.1056\/NEJMoa1908639","article-title":"Elexacaftor\u2013tezacaftor\u2013ivacaftor for cystic fibrosis with a single Phe508del allele","volume":"381","author":"Middleton","year":"2019","journal-title":"N Engl J Med"},{"key":"2026012204144277500_bib2","doi-asserted-by":"crossref","first-page":"e167957","DOI":"10.1172\/JCI167957","article-title":"Pharmacologic improvement of CFTR function rapidly decreases sputum pathogen density, but lung infections generally persist","volume":"133","author":"Nichols","year":"2023","journal-title":"J Clin Invest"},{"key":"2026012204144277500_bib3","doi-asserted-by":"crossref","first-page":"2301008","DOI":"10.1183\/13993003.01008-2023","article-title":"Long-term therapy with elexacaftor\/tezacaftor\/ivacaftor (ETI) in cystic fibrosis: improved clinical outcomes but infection and inflammation persist","volume":"62","author":"Tunney","year":"2023","journal-title":"Eur Respir J"},{"key":"2026012204144277500_bib4","doi-asserted-by":"crossref","first-page":"2622","DOI":"10.1182\/blood.2021014699","article-title":"Neutrophil dysfunction in the pathogenesis of cystic fibrosis","volume":"139","author":"Wang","year":"2022","journal-title":"Blood"},{"key":"2026012204144277500_bib5","doi-asserted-by":"crossref","first-page":"S30","DOI":"10.1002\/ppul.24129","article-title":"Inflammation in cystic fibrosis: an update","volume":"53","author":"Roesch","year":"2018","journal-title":"Pediatr Pulmonol"},{"key":"2026012204144277500_bib6","doi-asserted-by":"crossref","first-page":"e17553","DOI":"10.1016\/j.heliyon.2023.e17553","article-title":"Role of innate immunity and systemic inflammation in cystic fibrosis disease progression","volume":"9","author":"Purushothaman","year":"2023","journal-title":"Heliyon"},{"key":"2026012204144277500_bib7","doi-asserted-by":"crossref","first-page":"1693","DOI":"10.1056\/NEJMra2216474","article-title":"Cystic fibrosis","volume":"389","author":"Grasemann","year":"2023","journal-title":"N Engl J Med"},{"issue":"Suppl 1","key":"2026012204144277500_bib8","doi-asserted-by":"crossref","first-page":"S23","DOI":"10.1016\/j.jcf.2022.08.019","article-title":"Mucus aberrant properties in CF: insights from cells and animal models","volume":"22","author":"Ehre","year":"2023","journal-title":"J Cyst Fibros"},{"issue":"Suppl 3","key":"2026012204144277500_bib9","first-page":"S5","article-title":"Mucus obstruction and inflammation in early cystic fibrosis lung disease: emerging role of the IL-1 signaling pathway","volume":"54","author":"Bal\u00e1zs","year":"2019","journal-title":"Pediatr Pulmonol"},{"key":"2026012204144277500_bib10","doi-asserted-by":"crossref","first-page":"922","DOI":"10.1165\/rcmb.2010-0224OC","article-title":"Lack of cystic fibrosis transmembrane conductance regulator in CD3+ lymphocytes leads to aberrant cytokine secretion and hyperinflammatory adaptive immune responses","volume":"44","author":"Mueller","year":"2011","journal-title":"Am J Respir Cell Mol Biol"},{"key":"2026012204144277500_bib11","doi-asserted-by":"crossref","first-page":"9320","DOI":"10.1038\/s41598-018-27465-3","article-title":"Kcnn4 is a modifier gene of intestinal cystic fibrosis preventing lethality in the Cftr-F508del mouse","volume":"8","author":"Philp","year":"2018","journal-title":"Sci Rep"},{"key":"2026012204144277500_bib12","doi-asserted-by":"crossref","first-page":"G1032","DOI":"10.1152\/ajpgi.00473.2003","article-title":"Inflammation of the cystic fibrosis mouse small intestine","volume":"286","author":"Norkina","year":"2004","journal-title":"Am J Physiol Gastrointest Liver Physiol"},{"key":"2026012204144277500_bib13","doi-asserted-by":"crossref","first-page":"10791","DOI":"10.1038\/ncomms10791","article-title":"IL-1 receptor antagonist ameliorates inflammasome-dependent inflammation in murine and human cystic fibrosis","volume":"7","author":"Iannitti","year":"2016","journal-title":"Nat Commun"},{"key":"2026012204144277500_bib14","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.it.2020.11.004","article-title":"Succinate receptor 1: an emerging regulator of myeloid cell function in inflammation","volume":"42","author":"Krzak","year":"2021","journal-title":"Trends Immunol"},{"key":"2026012204144277500_bib15","doi-asserted-by":"crossref","first-page":"680","DOI":"10.1016\/j.tem.2021.06.003","article-title":"Rethinking succinate: an unexpected hormone-like metabolite in energy homeostasis","volume":"32","author":"Fern\u00e1ndez-Veledo","year":"2021","journal-title":"Trends Endocrinol Metab"},{"key":"2026012204144277500_bib16","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/j.immuni.2018.06.016","article-title":"Detection of succinate by intestinal tuft cells triggers a type 2 innate immune circuit","volume":"49","author":"Nadjsombati","year":"2018","journal-title":"Immunity"},{"key":"2026012204144277500_bib17","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1146\/annurev-immunol-042718-041505","article-title":"Tuft cells\u2014systemically dispersed sensory epithelia integrating immune and neural circuitry","volume":"37","author":"O\u2019Leary","year":"2019","journal-title":"Annu Rev Immunol"},{"key":"2026012204144277500_bib18","doi-asserted-by":"crossref","first-page":"1555","DOI":"10.1113\/JP282307","article-title":"Chemosensory cells in the respiratory tract as crucial regulators of innate immune responses","volume":"601","author":"Hollenhorst","year":"2023","journal-title":"J Physiol"},{"key":"2026012204144277500_bib19","doi-asserted-by":"crossref","first-page":"eadg8842","DOI":"10.1126\/sciadv.adg8842","article-title":"A succinate\/SUCNR1-brush cell defense program in the tracheal epithelium","volume":"9","author":"Perniss","year":"2023","journal-title":"Sci Adv"},{"key":"2026012204144277500_bib20","doi-asserted-by":"crossref","first-page":"683","DOI":"10.1016\/j.immuni.2020.03.005","article-title":"Chemosensory cell-derived acetylcholine drives tracheal mucociliary clearance in response to virulence-associated formyl peptides","volume":"52","author":"Perniss","year":"2020","journal-title":"Immunity"},{"key":"2026012204144277500_bib21","doi-asserted-by":"crossref","first-page":"1243","DOI":"10.1016\/j.immuni.2024.03.023","article-title":"Tuft cell-derived acetylcholine promotes epithelial chloride secretion and intestinal helminth clearance","volume":"57","author":"Billipp","year":"2024","journal-title":"Immunity"},{"key":"2026012204144277500_bib22","doi-asserted-by":"crossref","first-page":"eabj0474","DOI":"10.1126\/sciimmunol.abj0474","article-title":"Tuft cell\u2013produced cysteinyl leukotrienes and IL-25 synergistically initiate lung type 2 inflammation","volume":"6","author":"Ualiyeva","year":"2021","journal-title":"Sci Immunol"},{"key":"2026012204144277500_bib23","doi-asserted-by":"crossref","first-page":"e150951","DOI":"10.1172\/JCI150951","article-title":"Bitter taste signaling in tracheal epithelial brush cells elicits innate immune responses to bacterial infection","volume":"132","author":"Hollenhorst","year":"2022","journal-title":"J Clin Invest"},{"key":"2026012204144277500_bib24","doi-asserted-by":"crossref","first-page":"2221","DOI":"10.1016\/j.devcel.2022.08.010","article-title":"Pulmonary neuroendocrine cells sense succinate to stimulate myoepithelial cell contraction","volume":"57","author":"Yu","year":"2022","journal-title":"Dev Cell"},{"key":"2026012204144277500_bib25","doi-asserted-by":"crossref","first-page":"eaan8546","DOI":"10.1126\/science.aan8546","article-title":"Pulmonary neuroendocrine cells amplify allergic asthma responses","volume":"360","author":"Sui","year":"2018","journal-title":"Science"},{"key":"2026012204144277500_bib26","doi-asserted-by":"crossref","first-page":"eaav4634","DOI":"10.1126\/scitranslmed.aav4634","article-title":"CFTR-PTEN\u2013dependent mitochondrial metabolic dysfunction promotes Pseudomonas aeruginosa airway infection","volume":"11","author":"Riquelme","year":"2019","journal-title":"Sci Transl Med"},{"key":"2026012204144277500_bib27","article-title":"Airway succinate chemosensing induces CFTR-dependent anion secretion and mucus clearance which is impaired in cystic fibrosis [preprint]","author":"Apablaza","year":"2024"},{"key":"2026012204144277500_bib28","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1038\/s41586-018-0393-7","article-title":"A revised airway epithelial hierarchy includes CFTR-expressing ionocytes","volume":"560","author":"Montoro","year":"2018","journal-title":"Nature"},{"key":"2026012204144277500_bib29","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1111\/bph.15995","article-title":"Analysis of inhibitors of the anoctamin-1 chloride channel (transmembrane member 16A, TMEM16A) reveals indirect mechanisms involving alterations in calcium signalling","volume":"180","author":"Genovese","year":"2023","journal-title":"Br J Pharmacol"},{"key":"2026012204144277500_bib30","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1016\/j.ejphar.2016.04.007","article-title":"Pharmacological analysis of epithelial chloride secretion mechanisms in adult murine airways","volume":"781","author":"Gianotti","year":"2016","journal-title":"Eur J Pharmacol"},{"key":"2026012204144277500_bib31","doi-asserted-by":"crossref","first-page":"e75871","DOI":"10.7554\/eLife.75871","article-title":"Inhibition of the sodium-dependent HCO3 \u00a0\u2212 transporter SLC4A4, produces a cystic fibrosis-like airway disease phenotype","volume":"11","author":"Saint-Criq","year":"2022","journal-title":"Elife"},{"key":"2026012204144277500_bib32","first-page":"183","volume-title":"Human cell culture protocols. Methods in molecular medicine","author":"Fulcher","year":"2005","edition":"2nd ed."},{"key":"2026012204144277500_bib33","doi-asserted-by":"crossref","first-page":"C293","DOI":"10.1152\/ajpcell.1994.267.1.C293","article-title":"Anomalies in ion transport in CF mouse tracheal epithelium","volume":"267","author":"Grubb","year":"1994","journal-title":"Am J Physiol"},{"key":"2026012204144277500_bib34","doi-asserted-by":"crossref","first-page":"2312","DOI":"10.1183\/09031936.97.10102312","article-title":"Mucociliary clearance in cystic fibrosis knockout mice infected with Pseudomonas aeruginosa","volume":"10","author":"Cowley","year":"1997","journal-title":"Eur Respir J"},{"key":"2026012204144277500_bib35","doi-asserted-by":"crossref","first-page":"7410","DOI":"10.4049\/jimmunol.166.12.7410","article-title":"Transgenic cystic fibrosis mice exhibit reduced early clearance of Pseudomonas aeruginosa from the respiratory tract","volume":"166","author":"Schroeder","year":"2001","journal-title":"J Immunol"},{"key":"2026012204144277500_bib36","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1038\/s41586-018-0394-6","article-title":"A single-cell atlas of the airway epithelium reveals the CFTR-rich pulmonary ionocyte","volume":"560","author":"Plasschaert","year":"2018","journal-title":"Nature"},{"key":"2026012204144277500_bib37","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1038\/nature11130","article-title":"Reduced airway surface pH impairs bacterial killing in the porcine cystic fibrosis lung","volume":"487","author":"Pezzulo","year":"2012","journal-title":"Nature"},{"key":"2026012204144277500_bib38","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1164\/rccm.201812-2303LE","article-title":"SPLUNC1 loses its antimicrobial activity in acidic cystic fibrosis airway secretions","volume":"200","author":"Ahmad","year":"2019","journal-title":"Am J Respir Crit Care Med"},{"key":"2026012204144277500_bib39","doi-asserted-by":"crossref","first-page":"2101585","DOI":"10.1183\/13993003.01585-2021","article-title":"European Respiratory Society guidelines for the diagnosis of asthma in adults","volume":"60","author":"Louis","year":"2022","journal-title":"Eur Respir J"},{"key":"2026012204144277500_bib40","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1186\/s13223-020-0410-x","article-title":"Comparison of methacholine and mannitol challenges: importance of method of methacholine inhalation","volume":"16","author":"Cockcroft","year":"2020","journal-title":"Allergy Asthma Clin Immunol"},{"key":"2026012204144277500_bib41","doi-asserted-by":"crossref","first-page":"1102","DOI":"10.1016\/j.bbamcr.2008.02.005","article-title":"Localized cytosolic alkalization and its functional impact in ciliary cells","volume":"1783","author":"Lemberskiy-Kuzin","year":"2008","journal-title":"Biochim Biophys Acta"},{"key":"2026012204144277500_bib42","doi-asserted-by":"crossref","first-page":"21815","DOI":"10.1074\/jbc.M113.479360","article-title":"Role of tyrosine phosphorylation in the muscarinic activation of the cystic fibrosis transmembrane conductance regulator (CFTR)","volume":"288","author":"Billet","year":"2013","journal-title":"J Biol Chem"},{"key":"2026012204144277500_bib43","doi-asserted-by":"crossref","first-page":"e140076","DOI":"10.1172\/jci.insight.140076","article-title":"Lack of Kcnn4 improves mucociliary clearance in muco-obstructive lung disease","volume":"5","author":"Vega","year":"2020","journal-title":"JCI Insight"},{"key":"2026012204144277500_bib44","doi-asserted-by":"crossref","first-page":"e2307551120","DOI":"10.1073\/pnas.2307551120","article-title":"Dynamic regulation of airway surface liquid pH by TMEM16A and SLC26A4 in cystic fibrosis nasal epithelia with rare mutations","volume":"120","author":"Delpiano","year":"2023","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2026012204144277500_bib45","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1186\/s12576-022-00828-2","article-title":"Bicarbonate transport of airway surface epithelia in luminally perfused mice bronchioles","volume":"72","author":"Liu","year":"2022","journal-title":"J Physiol Sci"},{"key":"2026012204144277500_bib46","doi-asserted-by":"crossref","first-page":"3813","DOI":"10.1113\/jphysiol.2008.154468","article-title":"The Slc26a4 transporter functions as an electroneutral Cl\u2212\/I\u2212\/HCO3 \u00a0\u2212 exchanger: role of Slc26a4 and Slc26a6 in I\u2212 and HCO3 \u00a0\u2212 secretion and in regulation of CFTR in the parotid duct","volume":"586","author":"Shcheynikov","year":"2008","journal-title":"J Physiol"},{"key":"2026012204144277500_bib47","doi-asserted-by":"crossref","first-page":"497387","DOI":"10.1155\/2015\/497387","article-title":"Novel roles for chloride channels, exchangers, and regulators in chronic inflammatory airway diseases","volume":"2015","author":"Sala-Rabanal","year":"2015","journal-title":"Mediators Inflamm"},{"key":"2026012204144277500_bib48","doi-asserted-by":"crossref","first-page":"705","DOI":"10.1165\/rcmb.2018-0158OC","article-title":"Pendrin mediates bicarbonate secretion and enhances cystic fibrosis transmembrane conductance regulator function in airway surface epithelia","volume":"60","author":"Kim","year":"2019","journal-title":"Am J Respir Cell Mol Biol"},{"key":"2026012204144277500_bib49","doi-asserted-by":"crossref","first-page":"2200725","DOI":"10.1183\/13993003.00725-2022","article-title":"Elexacaftor\/tezacaftor\/ivacaftor corrects monocyte microbicidal deficiency in cystic fibrosis","volume":"61","author":"Cavinato","year":"2023","journal-title":"Eur Respir J"},{"key":"2026012204144277500_bib50","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1038\/s41590-019-0372-7","article-title":"SUCNR1 controls an anti-inflammatory program in macrophages to regulate the metabolic response to obesity","volume":"20","author":"Keiran","year":"2019","journal-title":"Nat Immunol"},{"key":"2026012204144277500_bib51","doi-asserted-by":"crossref","first-page":"1154","DOI":"10.2337\/db14-0346","article-title":"Targeted disruption of the SUCNR1 metabolic receptor leads to dichotomous effects on obesity","volume":"64","author":"McCreath","year":"2015","journal-title":"Diabetes"}],"container-title":["American Journal of Respiratory Cell and Molecular Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/ajrcmb\/article-pdf\/73\/5\/769\/66193512\/ajrcmb_73_5_769.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ajrcmb\/article-pdf\/73\/5\/769\/66193512\/ajrcmb_73_5_769.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,22]],"date-time":"2026-01-22T09:17:38Z","timestamp":1769073458000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ajrcmb\/article\/73\/5\/769\/8405085"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,1]]},"references-count":51,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2025,11,1]]},"published-print":{"date-parts":[[2025,11,1]]}},"URL":"https:\/\/doi.org\/10.1165\/rcmb.2024-0225oc","relation":{},"ISSN":["1044-1549","1535-4989"],"issn-type":[{"value":"1044-1549","type":"print"},{"value":"1535-4989","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2025,11]]},"published":{"date-parts":[[2025,11,1]]},"assertion":[{"value":"2024-05-10","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-04-16","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-10-31","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}