{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T23:25:18Z","timestamp":1793057118505,"version":"4.5.0"},"reference-count":141,"publisher":"American Physiological Society","issue":"5","funder":[{"DOI":"10.13039\/100001465","name":"American Thoracic Society","doi-asserted-by":"publisher","award":["ATS\/GSK Partnered Research Grant in Obstructive Lung Disease"],"award-info":[{"award-number":["ATS\/GSK Partnered Research Grant in Obstructive Lung Disease"]}],"id":[{"id":"10.13039\/100001465","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"HHS | NIH | National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["T32HL094296"],"award-info":[{"award-number":["T32HL094296"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000738","name":"U.S. Department of Veterans Affairs","doi-asserted-by":"publisher","award":["IK2BX003841"],"award-info":[{"award-number":["IK2BX003841"]}],"id":[{"id":"10.13039\/100000738","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.physiology.org"],"crossmark-restriction":true},"short-container-title":["American Journal of Physiology-Lung Cellular and Molecular Physiology"],"published-print":{"date-parts":[[2023,5,1]]},"abstract":"<jats:p> Club cells are found in human small airways where they play an important role in immune defense, xenobiotic metabolism, and repair after injury. Over the past few years, data from single-cell RNA sequencing (scRNA-seq) studies has generated new insights into club cell heterogeneity and function. In this review, we integrate findings from scRNA-seq experiments with earlier in vitro, in vivo, and microscopy studies and highlight the many ways club cells contribute to airway homeostasis. We then discuss evidence for loss of club cells or club cell products in the airways of patients with chronic obstructive pulmonary disease (COPD) and discuss potential mechanisms through which this might occur. <\/jats:p>","DOI":"10.1152\/ajplung.00192.2022","type":"journal-article","created":{"date-parts":[[2023,3,21]],"date-time":"2023-03-21T12:00:57Z","timestamp":1679400057000},"page":"L652-L665","update-policy":"https:\/\/doi.org\/10.1152\/aps-crossmark-policy","source":"Crossref","is-referenced-by-count":54,"title":["An update in club cell biology and its potential relevance to chronic obstructive pulmonary disease"],"prefix":"10.1152","volume":"324","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7268-6783","authenticated-orcid":false,"given":"Jessica B.","family":"Blackburn","sequence":"first","affiliation":[{"name":"Department of Veterans Affairs Medical Center, Nashville, Tennessee, United States"},{"name":"Division of Allergy, Pulmonary, and Critical Care Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ngan Fung","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2715-5163","authenticated-orcid":false,"given":"Nathan W.","family":"Bartlett","sequence":"additional","affiliation":[{"name":"Viral Immunology and Respiratory Disease Group, University of Newcastle, Callaghan, New South Wales, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6200-5235","authenticated-orcid":false,"given":"Bradley W.","family":"Richmond","sequence":"additional","affiliation":[{"name":"Department of Veterans Affairs Medical Center, Nashville, Tennessee, United States"},{"name":"Division of Allergy, Pulmonary, and Critical Care Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee, United States"},{"name":"Department of Cell and Developmental Biology, Vanderbilt University, Nashville, Tennessee, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"24","reference":[{"key":"B1","first-page":"1","volume":"16","author":"K\u00f6lliker A","year":"1881","journal-title":"Verh Physik Med Ges Wurzburg"},{"key":"B2","first-page":"321","volume":"41","author":"Clara M","year":"1937","journal-title":"Z mikrosk anat Forsch"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1183\/09031936.00146609"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1164\/arrd.1966.93.6.946"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1016\/0014-4827(56)90093-3"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1002\/jmor.1051280203"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.3109\/01902148009069646"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.3109\/01902148009069645"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.3109\/01902148009069644"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1016\/s0022-5320(74)90052-5"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1177\/32.1.6418790"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1016\/0009-8981(93)90077-h"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1016\/0009-8981(92)90122-7"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(20)80734-0"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.2000.tb05549.x"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1177\/36.1.3275712"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1164\/ajrccm.159.5.9806044"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1007\/BF00191438"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1172\/JCI117028"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.1995.268.4.L565"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201804-0734OC"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.90558"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-018-0394-6"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-018-0096-5"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201710-2107OC"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.aaw3413"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-019-0468-5"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2018-214865"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201712-2410OC"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.aba1983"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201911-2199OC"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-16239-z"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.aba1972"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2922-4"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.62522"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1186\/s12931-020-01442-9"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.abe4282"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.15252\/embj.20105114"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-019-0750-6"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.202008-3198OC"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1038\/s41525-021-00237-1"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22147646"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-021-01332-7"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1038\/s41422-020-00455-9"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-021-03570-8"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.15252\/emmm.202012871"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-022-04552-0"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-022-04541-3"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.202207-1384OC"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.1995.269.6.L800"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.2000.278.6.L1256"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201005-0744OC"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.124732"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2021.11.012"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.1016\/j.biocel.2009.09.002"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.5114\/kitp.2016.58961"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.1038\/269713a0"},{"key":"B58","first-page":"558","volume":"86","author":"Mahvi D","year":"1977","journal-title":"Am J Pathol"},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.1995.269.6.L791"},{"key":"B60","first-page":"314","volume":"27","author":"Lund J","year":"1985","journal-title":"Mol Pharmacol"},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.1996.271.4.L656"},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.1007\/s00204-016-1868-7"},{"key":"B63","doi-asserted-by":"publisher","DOI":"10.1165\/ajrcmb.17.2.2676"},{"key":"B64","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.1998.275.2.L348"},{"key":"B65","doi-asserted-by":"publisher","DOI":"10.1183\/09031936.00134214"},{"key":"B66","doi-asserted-by":"publisher","DOI":"10.1038\/335726a0"},{"key":"B67","doi-asserted-by":"publisher","DOI":"10.1165\/ajrcmb.12.2.7865218"},{"key":"B68","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.1998.275.5.L924"},{"key":"B69","doi-asserted-by":"publisher","DOI":"10.1159\/000450788"},{"key":"B70","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2021-0548OC"},{"key":"B71","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms11240"},{"key":"B72","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2017-0329OC"},{"key":"B73","doi-asserted-by":"publisher","DOI":"10.1038\/s41385-020-00344-9"},{"key":"B74","first-page":"361","volume":"12","author":"Abboud RT","year":"2008","journal-title":"Int J Tuberc Lung Dis"},{"key":"B75","first-page":"706","volume":"58","author":"Inayama Y","year":"1988","journal-title":"Lab Invest"},{"key":"B76","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.1994.266.3.L296"},{"key":"B77","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00155.2003"},{"key":"B78","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0906850106"},{"key":"B79","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2009.04.002"},{"key":"B80","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-018-0393-7"},{"key":"B81","first-page":"219","volume":"57","author":"Brody AR","year":"1987","journal-title":"Lab Invest"},{"key":"B82","doi-asserted-by":"publisher","DOI":"10.1165\/ajrcmb\/4.6.544"},{"key":"B83","doi-asserted-by":"publisher","DOI":"10.1038\/nature12777"},{"key":"B84","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)64169-7"},{"key":"B85","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2005.03.032"},{"key":"B86","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2019.12.014"},{"key":"B87","doi-asserted-by":"publisher","DOI":"10.1038\/s41421-019-0132-8"},{"key":"B88","doi-asserted-by":"publisher","DOI":"10.15252\/embj.2019102099"},{"key":"B89","first-page":"127","volume":"62","author":"Cutz E","year":"1971","journal-title":"Am J Pathol"},{"key":"B90","doi-asserted-by":"publisher","DOI":"10.1177\/44.12.8985135"},{"key":"B91","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201608-1672OC"},{"key":"B92","doi-asserted-by":"publisher","DOI":"10.1016\/j.coph.2004.01.011"},{"key":"B93","doi-asserted-by":"publisher","DOI":"10.1515\/jtim-2015-0013"},{"key":"B94","doi-asserted-by":"publisher","DOI":"10.1136\/thoraxjnl-2020-216037"},{"key":"B95","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2004-0060OC"},{"key":"B96","doi-asserted-by":"publisher","DOI":"10.1172\/JCI29176"},{"key":"B97","doi-asserted-by":"publisher","DOI":"10.1172\/JCI25167"},{"key":"B98","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2009-0304OC"},{"key":"B99","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)64727-X"},{"key":"B100","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.200204-285OC"},{"key":"B101","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1204710109"},{"key":"B102","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1900500"},{"key":"B103","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1106955"},{"key":"B104","doi-asserted-by":"publisher","DOI":"10.1038\/nm.2971"},{"key":"B105","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM196806202782501"},{"key":"B106","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa032158"},{"key":"B107","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201010-1629OC"},{"key":"B108","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201604-0759OC"},{"key":"B109","doi-asserted-by":"publisher","DOI":"10.1172\/JCI60324"},{"key":"B110","doi-asserted-by":"publisher","DOI":"10.1038\/nrdp.2015.76"},{"key":"B111","doi-asserted-by":"publisher","DOI":"10.1186\/s12931-019-1017-y"},{"key":"B112","doi-asserted-by":"publisher","DOI":"10.1136\/thx.39.11.844"},{"key":"B113","doi-asserted-by":"publisher","DOI":"10.1164\/arrd.1975.111.1.4"},{"key":"B114","doi-asserted-by":"publisher","DOI":"10.1183\/09031936.93.05101231"},{"key":"B115","doi-asserted-by":"publisher","DOI":"10.1183\/09031936.97.10051108"},{"key":"B116","doi-asserted-by":"publisher","DOI":"10.1164\/ajrccm.163.1.9912137"},{"key":"B117","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.200503-456OC"},{"key":"B118","doi-asserted-by":"publisher","DOI":"10.1155\/2014\/216465"},{"key":"B119","doi-asserted-by":"publisher","DOI":"10.1183\/09031936.01.17509460"},{"key":"B120","doi-asserted-by":"publisher","DOI":"10.1172\/JCI10259"},{"key":"B121","doi-asserted-by":"publisher","DOI":"10.1016\/s0012-3692(15)51033-7"},{"key":"B122","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.90369.2008"},{"key":"B123","doi-asserted-by":"publisher","DOI":"10.1016\/S0007-0971(66)80044-X"},{"key":"B124","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-physiol-022516-034314"},{"key":"B125","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201810-1975TR"},{"key":"B126","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2021.645593"},{"key":"B127","doi-asserted-by":"publisher","DOI":"10.3390\/biom10030420"},{"key":"B128","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2018.03.009"},{"key":"B129","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2017-0390OC"},{"key":"B130","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201406-1167LE"},{"key":"B131","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-54292-x"},{"key":"B132","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2020.03.047"},{"key":"B133","doi-asserted-by":"publisher","DOI":"10.1186\/1465-9921-15-11"},{"key":"B134","doi-asserted-by":"publisher","DOI":"10.1136\/thoraxjnl-2017-210593"},{"key":"B135","doi-asserted-by":"publisher","DOI":"10.3109\/01902140903019710"},{"key":"B136","doi-asserted-by":"publisher","DOI":"10.1172\/JCI125669"},{"key":"B137","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201704-0667OC"},{"key":"B138","doi-asserted-by":"publisher","DOI":"10.1164\/ajrccm.157.3.9709027"},{"key":"B139","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra0804752"},{"key":"B140","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.87536"},{"key":"B141","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2020-0149MA"}],"container-title":["American Journal of Physiology-Lung Cellular and Molecular Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.physiology.org\/doi\/pdf\/10.1152\/ajplung.00192.2022","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,4,13]],"date-time":"2023-04-13T19:35:48Z","timestamp":1681414548000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.physiology.org\/doi\/10.1152\/ajplung.00192.2022"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,5,1]]},"references-count":141,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2023,5,1]]}},"alternative-id":["10.1152\/ajplung.00192.2022"],"URL":"https:\/\/doi.org\/10.1152\/ajplung.00192.2022","relation":{},"ISSN":["1040-0605","1522-1504"],"issn-type":[{"value":"1040-0605","type":"print"},{"value":"1522-1504","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,5,1]]},"assertion":[{"value":"2022-06-20","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-03-10","order":1,"name":"revised","label":"Revised","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-03-16","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-04-13","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}