{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T15:33:14Z","timestamp":1790695994279,"version":"4.1.0"},"reference-count":50,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2017,8,1]],"date-time":"2017-08-01T00:00:00Z","timestamp":1501545600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2017,8,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Repair of the lung epithelium after injury is a critical component for resolution; however, the processes necessary to drive epithelial resolution are not clearly defined. Published data demonstrate that Foxp3+ regulatory T cells (Tregs) enhance alveolar epithelial proliferation after injury, and Tregs in vitro directly promote type II alveolar epithelial cell (AT2) proliferation, in part by a contact-independent mechanism. Therefore, we sought to determine the contribution of Treg-specific expression of a growth factor that is known to be important in lung repair, keratinocyte growth factor (kgf). The data demonstrate that Tregs express kgf and that Treg-specific expression of kgf regulates alveolar epithelial proliferation during the resolution phase of acute lung injury and in a model of regenerative alveologenesis in vivo. In vitro experiments demonstrate that AT2 cells cocultured with Tregs lacking kgf have decreased rates of proliferation compared with AT2 cells cocultured with wild-type Tregs. Moreover, Tregs isolated from lung tissue and grown in culture express higher levels of two growth factors that are important for lung repair (kgf and amphiregulin) compared with Tregs isolated from splenic tissue. Lastly, Tregs isolated from human lung tissue can be stimulated ex vivo to induce kgf expression. This study reveals mechanisms by which Tregs direct tissue-reparative effects during resolution after acute lung injury, further supporting the emerging role of Tregs in tissue repair.<\/jats:p>","DOI":"10.1165\/rcmb.2017-0019oc","type":"journal-article","created":{"date-parts":[[2017,3,15]],"date-time":"2017-03-15T14:40:54Z","timestamp":1489588854000},"page":"162-173","source":"Crossref","is-referenced-by-count":113,"title":["Foxp3+ Regulatory T Cell Expression of Keratinocyte Growth Factor Enhances Lung Epithelial Proliferation"],"prefix":"10.1093","volume":"57","author":[{"given":"Catherine F.","family":"Dial","sequence":"first","affiliation":[{"name":"Division of Pulmonary Diseases and Critical Care Medicine, Department of Medicine"},{"name":"Marsico Lung Institute, University of North Carolina, Chapel Hill, North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miriya K.","family":"Tune","sequence":"additional","affiliation":[{"name":"Division of Pulmonary Diseases and Critical Care Medicine, Department of Medicine"},{"name":"Marsico Lung Institute, University of North Carolina, Chapel Hill, North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claire M.","family":"Doerschuk","sequence":"additional","affiliation":[{"name":"Division of Pulmonary Diseases and Critical Care Medicine, Department of Medicine"},{"name":"Marsico Lung Institute, University of North Carolina, Chapel Hill, North Carolina"},{"name":"Center for Airways Disease, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason R.","family":"Mock","sequence":"additional","affiliation":[{"name":"Division of Pulmonary Diseases and Critical Care Medicine, Department of Medicine"},{"name":"Marsico Lung Institute, University of North Carolina, Chapel Hill, North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2017,8,1]]},"reference":[{"key":"2026021122461223300_bib1","doi-asserted-by":"crossref","first-page":"824","DOI":"10.1164\/rccm.201206-1063PP","article-title":"Respiratory infection and the impact of pulmonary immunity on lung health and disease","volume":"186","author":"Mizgerd","year":"2012","journal-title":"Am J Respir Crit Care Med"},{"key":"2026021122461223300_bib2","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1172\/JCI0211638","article-title":"Phosphatidylserine-dependent ingestion of apoptotic cells promotes TGF-\u03b21 secretion and the resolution of inflammation","volume":"109","author":"Huynh","year":"2002","journal-title":"J Clin Invest"},{"key":"2026021122461223300_bib3","doi-asserted-by":"crossref","first-page":"1145","DOI":"10.1111\/j.1523-1755.2004.00487.x","article-title":"Lipoxins: potential anti-inflammatory, proresolution, and antifibrotic mediators in renal disease","volume":"65","author":"Kieran","year":"2004","journal-title":"Kidney Int"},{"key":"2026021122461223300_bib4","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1002\/jlb.61.4.375","article-title":"Apoptosis in resolution of inflammation","volume":"61","author":"Savill","year":"1997","journal-title":"J Leukoc Biol"},{"key":"2026021122461223300_bib5","doi-asserted-by":"crossref","first-page":"1191","DOI":"10.1038\/ni1276","article-title":"Resolution of inflammation: the beginning programs the end","volume":"6","author":"Serhan","year":"2005","journal-title":"Nat Immunol"},{"key":"2026021122461223300_bib6","doi-asserted-by":"crossref","first-page":"9286","DOI":"10.1073\/pnas.0900668106","article-title":"Stem cells are dispensable for lung homeostasis but restore airways after injury","volume":"106","author":"Giangreco","year":"2009","journal-title":"Proc Natl Acad Sci USA"},{"key":"2026021122461223300_bib7","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1165\/ajrcmb.24.6.4498","article-title":"Clara cell secretory protein-expressing cells of the airway neuroepithelial body microenvironment include a label-retaining subset and are critical for epithelial renewal after progenitor cell depletion","volume":"24","author":"Hong","year":"2001","journal-title":"Am J Respir Cell Mol Biol"},{"key":"2026021122461223300_bib8","first-page":"L1031","article-title":"Cell cycle kinetics in the alveolar epithelium","volume":"272","author":"Uhal","year":"1997","journal-title":"Am J Physiol"},{"key":"2026021122461223300_bib9","first-page":"317","article-title":"Alterations in cell proliferation in mouse lung following urethane exposure. 3. 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