{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T17:47:51Z","timestamp":1783705671969,"version":"3.55.0"},"reference-count":81,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2021,12,1]],"date-time":"2021-12-01T00:00:00Z","timestamp":1638316800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100008385","name":"Fondazione per la Ricerca sulla Fibrosi Cistica","doi-asserted-by":"publisher","award":["13\/2018,12\/2019, 9\/2020"],"award-info":[{"award-number":["13\/2018,12\/2019, 9\/2020"]}],"id":[{"id":"10.13039\/501100008385","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000897","name":"Cystic Fibrosis Foundation","doi-asserted-by":"publisher","award":["Assael08A0"],"award-info":[{"award-number":["Assael08A0"]}],"id":[{"id":"10.13039\/100000897","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Lega Italiana Fibrosi Cistica ONLUS - LIFC","award":["001"],"award-info":[{"award-number":["001"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Cystic fibrosis in characterized by pulmonary bacterial colonization and hyperinflammation. Lymphocytes, monocytes\/macrophages, neutrophils, and dendritic cells of patients with CF express functional CFTR and are directly affected by altered CFTR expression\/function, impairing their ability to resolve infections and inflammation. However, the mechanism behind and the contribution of leukocytes in the pathogenesis of CF are still poorly characterized. The recent clinical introduction of specific CFTR modulators added an important tool not only for the clinical management of the disease but also to the investigation of the pathophysiological mechanisms related to CFTR dysfunction and dysregulated immunity. These drugs treat the basic defect in cystic fibrosis (CF) by increasing CFTR function with improvement of lung function and quality of life, and may improve clinical outcomes also by correcting the dysregulated immune function that characterizes CF. Measure of CFTR function, protein expression profiling and several omics methods were used to identify molecular changes in freshly isolated leukocytes of CF patients, highlighting two roles of leukocytes in CF: one more generally related to the mechanism(s) causing immune dysregulation in CF and unresolved inflammation, and another more applicative role, which identifies in myeloid cells, an important tool predictive of the therapeutic response of CF patients. In this review we will summarize available data on CFTR expression and function in leukocyte populations and will discuss potential clinical applications based on available data.<\/jats:p>","DOI":"10.3390\/cells10123380","type":"journal-article","created":{"date-parts":[[2021,12,1]],"date-time":"2021-12-01T05:02:36Z","timestamp":1638334956000},"page":"3380","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Revisiting the Role of Leukocytes in Cystic Fibrosis"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9463-7533","authenticated-orcid":false,"given":"Monica","family":"Averna","sequence":"first","affiliation":[{"name":"Department of Experimental Medicine (DIMES), University of Genova, 16132 Genova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola","family":"Melotti","sequence":"additional","affiliation":[{"name":"Cystic Fibrosis Centre, Azienda Ospedaliera Universitaria Integrata Verona, 37126 Verona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2739-4014","authenticated-orcid":false,"given":"Claudio","family":"Sorio","sequence":"additional","affiliation":[{"name":"Department of Medicine, General Pathology Division, University of Verona, 37134 Verona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,12,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1056\/NEJMra1300109","article-title":"Origins of cystic fibrosis lung disease","volume":"372","author":"Stoltz","year":"2015","journal-title":"N. Engl. J. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1007\/s12016-007-8039-9","article-title":"Chronic inflammation in the cystic fibrosis lung: Alterations in inter- and intracellular signaling","volume":"34","author":"Nichols","year":"2008","journal-title":"Clin. Rev. Allergy Immunol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1007\/s00005-011-0113-6","article-title":"The cystic fibrosis neutrophil: A specialized yet potentially defective cell","volume":"59","author":"Hayes","year":"2011","journal-title":"Arch. Immunol. Ther. Exp."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1159\/000346568","article-title":"Cystic fibrosis transmembrane conductance regulator recruitment to phagosomes in neutrophils","volume":"5","author":"Zhou","year":"2013","journal-title":"J. Innate Immunol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"999","DOI":"10.1182\/blood-2014-02-555268","article-title":"A neutrophil intrinsic impairment affecting Rab27a and degranulation in cystic fibrosis is corrected by CFTR potentiator therapy","volume":"124","author":"Pohl","year":"2014","journal-title":"Blood"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1002\/JLB.5HI1117-454RR","article-title":"Frontline Science: Pathological conditioning of human neutrophils recruited to the airway milieu in cystic fibrosis","volume":"104","author":"Forrest","year":"2018","journal-title":"J. Leukoc. Biol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"4335","DOI":"10.1073\/pnas.0712386105","article-title":"Profound functional and signaling changes in viable inflammatory neutrophils homing to cystic fibrosis airways","volume":"105","author":"Tirouvanziam","year":"2008","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"5779","DOI":"10.1073\/pnas.0813410106","article-title":"Activation of critical, host-induced, metabolic and stress pathways marks neutrophil entry into cystic fibrosis lungs","volume":"106","author":"Makam","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Corti, A., Franzini, M., Cianchetti, S., Bergamini, G., Lorenzini, E., Melotti, P., Paolicchi, A., Paggiaro, P., and Pompella, A. (2012). Contribution by polymorphonucleate granulocytes to elevated gamma-glutamyltransferase in cystic fibrosis sputum. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0034772"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1164\/rccm.201305-0908LE","article-title":"Glutathione inhalation treatments in cystic fibrosis: The interference of airway gamma-glutamyltransferase","volume":"189","author":"Corti","year":"2014","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1016\/j.jcf.2016.12.002","article-title":"Increasing sputum levels of gamma-glutamyltransferase may identify cystic fibrosis patients who do not benefit from inhaled glutathione","volume":"16","author":"Corti","year":"2017","journal-title":"J. Cyst. Fibros."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1039\/c2ib00127f","article-title":"MudPIT analysis of released proteins in Pseudomonas aeruginosa laboratory and clinical strains in relation to pro-inflammatory effects","volume":"4","author":"Bergamini","year":"2012","journal-title":"Integr. Biol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1159\/000417617","article-title":"Polymorphonuclear leukocyte elastase: Its effects on the pathogenesis of Pseudomonas aeruginosa infection in cystic fibrosis","volume":"42","author":"Doring","year":"1989","journal-title":"Antibiot. Chemother."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1423","DOI":"10.1038\/nm1690","article-title":"Cleavage of CXCR1 on neutrophils disables bacterial killing in cystic fibrosis lung disease","volume":"13","author":"Hartl","year":"2007","journal-title":"Nat. Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"969","DOI":"10.1183\/09031936.00194611","article-title":"Efficacy, safety and effect on biomarkers of AZD9668 in cystic fibrosis","volume":"40","author":"Elborn","year":"2012","journal-title":"Eur. Respir. J."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1183\/09031936.00047306","article-title":"alpha1-Antitrypsin inhalation reduces airway inflammation in cystic fibrosis patients","volume":"29","author":"Griese","year":"2007","journal-title":"Eur. Respir. J."},{"key":"ref_17","first-page":"CD001127","article-title":"Dornase alfa for cystic fibrosis","volume":"9","author":"Yang","year":"2018","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1136\/thoraxjnl-2017-210134","article-title":"Delayed neutrophil apoptosis enhances NET formation in cystic fibrosis","volume":"73","author":"Gray","year":"2018","journal-title":"Thorax"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/j.jcf.2015.02.010","article-title":"Alterations in blood leukocytes of G551D-bearing cystic fibrosis patients undergoing treatment with ivacaftor","volume":"15","author":"Bratcher","year":"2016","journal-title":"J. Cyst. Fibros."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2002161","DOI":"10.1183\/13993003.02161-2020","article-title":"Ivacaftor modifies cystic fibrosis neutrophil phenotype in subjects with R117H residual function CFTR mutations","volume":"57","author":"Hardisty","year":"2021","journal-title":"Eur. Respir. J."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"933","DOI":"10.1038\/ncb1456","article-title":"CFTR regulates phagosome acidification in macrophages and alters bactericidal activity","volume":"8","author":"Di","year":"2006","journal-title":"Nat. Cell Biol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"31422","DOI":"10.1074\/jbc.M705296200","article-title":"Cystic fibrosis transmembrane conductance regulator-independent phagosomal acidification in macrophages","volume":"282","author":"Haggie","year":"2007","journal-title":"J. Biol. Chem."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"3825","DOI":"10.1099\/mic.0.2008\/023200-0","article-title":"Burkholderia cenocepacia-induced delay of acidification and phagolysosomal fusion in cystic fibrosis transmembrane conductance regulator (CFTR)-defective macrophages","volume":"154","author":"Lamothe","year":"2008","journal-title":"Microbiology"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"10260","DOI":"10.1021\/bi060490t","article-title":"CFTR Expression in human neutrophils and the phagolysosomal chlorination defect in cystic fibrosis","volume":"45","author":"Painter","year":"2006","journal-title":"Biochemistry"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1345","DOI":"10.1189\/jlb.0907658","article-title":"The role of chloride anion and CFTR in killing of Pseudomonas aeruginosa by normal and CF neutrophils","volume":"83","author":"Painter","year":"2008","journal-title":"J. Leukoc. Biol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1871","DOI":"10.3389\/fimmu.2020.01871","article-title":"Consequences of CRISPR-Cas9-Mediated CFTR Knockout in Human Macrophages","volume":"11","author":"Zhang","year":"2020","journal-title":"Front. Immunol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1189\/jlb.1108699","article-title":"Pivotal Advance: Expansion of small sputum macrophages in CF: Failure to express MARCO and mannose receptors","volume":"86","author":"Wright","year":"2009","journal-title":"J. Leukoc. Biol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1189\/jlb.0309120","article-title":"Editorial: The role of macrophages and their scavenger receptors in cystic fibrosis","volume":"86","author":"Sorio","year":"2009","journal-title":"J. Leukoc. Biol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1165\/rcmb.2008-0170OC","article-title":"Macrophages directly contribute to the exaggerated inflammatory response in cystic fibrosis transmembrane conductance regulator-\/- mice","volume":"40","author":"Bruscia","year":"2009","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1111","DOI":"10.1189\/jlb.0412188","article-title":"Absence of the cystic fibrosis transmembrane regulator (Cftr) from myeloid-derived cells slows resolution of inflammation and infection","volume":"92","author":"Bonfield","year":"2012","journal-title":"J. Leukoc. Biol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1381","DOI":"10.1164\/rccm.201905-1013OC","article-title":"Specific Inhibition of the NLRP3 Inflammasome as an Antiinflammatory Strategy in Cystic Fibrosis","volume":"200","author":"McElvaney","year":"2019","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1801771","DOI":"10.1183\/13993003.01771-2018","article-title":"The cumulative effect of inflammation and infection on structural lung disease in early cystic fibrosis","volume":"54","author":"Rosenow","year":"2019","journal-title":"Eur. Respir. J."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"e49248","DOI":"10.7554\/eLife.49248","article-title":"ENaC-mediated sodium influx exacerbates NLRP3-dependent inflammation in cystic fibrosis","volume":"8","author":"Scambler","year":"2019","journal-title":"eLife"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1016\/j.jcf.2019.08.021","article-title":"Whole-blood transcriptomic responses to lumacaftor\/ivacaftor therapy in cystic fibrosis","volume":"19","author":"Kopp","year":"2020","journal-title":"J. Cyst. Fibros."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"e54556","DOI":"10.7554\/eLife.54556","article-title":"Different CFTR modulator combinations downregulate inflammation differently in cystic fibrosis","volume":"9","author":"Scambler","year":"2020","journal-title":"eLife"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"581","DOI":"10.3389\/fimmu.2020.00581","article-title":"Resolvin D1 reduces lung infection and inflammation activating resolution in cystic fibrosis","volume":"11","author":"Isopi","year":"2020","journal-title":"Front. Immunol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1129","DOI":"10.3389\/fphar.2020.01129","article-title":"The resolution approach to cystic fibrosis inflammation","volume":"11","author":"Recchiuti","year":"2020","journal-title":"Front. Pharmacol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/j.gendis.2019.07.012","article-title":"Leukocyte adhesion defect: Where do we stand circa 2019?","volume":"7","author":"Das","year":"2020","journal-title":"Genes Dis."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1123","DOI":"10.1164\/rccm.201510-1922OC","article-title":"Mutations of cystic fibrosis transmembrane conductance regulator gene cause a monocyte-selective adhesion deficiency","volume":"193","author":"Sorio","year":"2016","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1016\/j.jcf.2017.03.007","article-title":"Monocyte derived macrophages from CF pigs exhibit increased inflammatory responses at birth","volume":"16","author":"Paemka","year":"2017","journal-title":"J. Cyst. Fibros."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1007\/978-1-61779-120-8_19","article-title":"Comparative biology of cystic fibrosis animal models","volume":"742","author":"Fisher","year":"2011","journal-title":"Methods Mol. Biol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1837","DOI":"10.1126\/science.1163600","article-title":"Disruption of the CFTR gene produces a model of cystic fibrosis in newborn pigs","volume":"321","author":"Rogers","year":"2008","journal-title":"Science"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"3149","DOI":"10.1172\/JCI43052","article-title":"Disease phenotype of a ferret CFTR-knockout model of cystic fibrosis","volume":"120","author":"Sun","year":"2010","journal-title":"J. Clin. Investig."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"29ps20","DOI":"10.1126\/scitranslmed.3001130","article-title":"The development of lung disease in cystic fibrosis pigs","volume":"2","author":"Wine","year":"2010","journal-title":"Sci. Transl. Med."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Favia, M., Gallo, C., Guerra, L., De Venuto, D., Diana, A., Polizzi, A.M., Montemurro, P., Mariggio, M.A., Leonetti, G., and Manca, A. (2020). Treatment of Cystic Fibrosis Patients Homozygous for F508del with Lumacaftor-Ivacaftor (Orkambi((R))) Restores Defective CFTR Channel Function in Circulating Mononuclear Cells. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21072398"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1002\/cyto.a.22456","article-title":"Detection of CFTR protein in human leukocytes by flow cytometry","volume":"85","author":"Johansson","year":"2014","journal-title":"Cytometry A"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Pedrazzi, M., Vercellone, S., Barberis, E., Capraro, M., De Tullio, R., Cresta, F., Casciaro, R., Castellani, C., Patrone, M., and Marengo, E. (2021). Identification of Potential Leukocyte Biomarkers Related to Drug Recovery of CFTR: Clinical Applications in Cystic Fibrosis. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22083928"},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Sorio, C., Buffelli, M., Angiari, C., Ettorre, M., Johansson, J., Vezzalini, M., Viviani, L., Ricciardi, M., Verze, G., and Assael, B.M. (2011). Defective CFTR expression and function are detectable in blood monocytes: Development of a new blood test for cystic fibrosis. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0022212"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"3242","DOI":"10.1016\/S0021-9258(19)50722-0","article-title":"Human lymphocytes transcribe the cystic fibrosis transmembrane conductance regulator gene and exhibit CF-defective cAMP-regulated chloride current","volume":"267","author":"McDonald","year":"1992","journal-title":"J. Biol. Chem."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1136\/thoraxjnl-2011-200585","article-title":"Distinct patterns of inflammation in the airway lumen and bronchial mucosa of children with cystic fibrosis","volume":"67","author":"Regamey","year":"2012","journal-title":"Thorax"},{"key":"ref_51","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":"ref_52","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1164\/rccm.201206-1150OC","article-title":"A Th17- and Th2-skewed cytokine profile in cystic fibrosis lungs represents a potential risk factor for Pseudomonas aeruginosa infection","volume":"187","author":"Tiringer","year":"2013","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1164\/rccm.201207-1346OC","article-title":"Th17\/Treg imbalance in murine cystic fibrosis is linked to indoleamine 2,3-dioxygenase deficiency but corrected by kynurenines","volume":"187","author":"Iannitti","year":"2013","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"914","DOI":"10.1164\/rccm.201407-1381OC","article-title":"Regulatory T-cell impairment in cystic fibrosis patients with chronic pseudomonas infection","volume":"191","author":"Hector","year":"2015","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Mulcahy, E.M., Hudson, J.B., Beggs, S.A., Reid, D.W., Roddam, L.F., and Cooley, M.A. (2015). High peripheral blood th17 percent associated with poor lung function in cystic fibrosis. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0120912"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1159\/000362984","article-title":"Invariant natural killer T (iNKT) cells prevent autoimmunity, but induce pulmonary inflammation in cystic fibrosis","volume":"34","author":"Siegmann","year":"2014","journal-title":"Cell Physiol. Biochem."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"416","DOI":"10.1111\/imcb.12230","article-title":"Widespread alterations in the peripheral blood innate immune cell profile in cystic fibrosis reflect lung pathology","volume":"97","author":"Mulcahy","year":"2019","journal-title":"Immunol. Cell Biol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1694","DOI":"10.1038\/sj.mt.6300210","article-title":"Activation of CFTR-specific T Cells in cystic fibrosis mice following gene transfer","volume":"15","author":"Limberis","year":"2007","journal-title":"Mol. Ther."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1089\/humc.2012.249","article-title":"Self-reactive CFTR T cells in humans: Implications for gene therapy","volume":"24","author":"Calcedo","year":"2013","journal-title":"Hum. Gene Ther. Clin. Dev."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1186\/s12931-019-1103-1","article-title":"CFTR regulates B cell activation and lymphoid follicle development","volume":"20","author":"Polverino","year":"2019","journal-title":"Respir. Res."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1161\/01.RES.0000252802.25497.b7","article-title":"Platelets as immune cells: Bridging inflammation and cardiovascular disease","volume":"100","author":"Weber","year":"2007","journal-title":"Circ. Res."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"4635","DOI":"10.1182\/blood-2004-06-2098","article-title":"Platelet activation in cystic fibrosis","volume":"105","author":"Linden","year":"2005","journal-title":"Blood"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"3970","DOI":"10.1096\/fj.10-159921","article-title":"Cystic fibrosis transmembrane conductance regulator (CFTR) expression in human platelets: Impact on mediators and mechanisms of the inflammatory response","volume":"24","author":"Mattoscio","year":"2010","journal-title":"FASEB J."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1164\/rccm.200508-1243PP","article-title":"The inflammatory role of platelets in cystic fibrosis","volume":"173","author":"Michelson","year":"2006","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"2041","DOI":"10.1172\/JCI129635","article-title":"Cystic fibrosis transmembrane conductance regulator dysfunction in platelets drives lung hyperinflammation","volume":"130","author":"Yu","year":"2020","journal-title":"J. Clin. Investig."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1164\/rccm.201404-0703OC","article-title":"Clinical mechanism of the cystic fibrosis transmembrane conductance regulator potentiator ivacaftor in G551D-mediated cystic fibrosis","volume":"190","author":"Rowe","year":"2014","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1617","DOI":"10.1164\/rccm.201609-1954OC","article-title":"Restoring Cystic Fibrosis Transmembrane Conductance Regulator Function Reduces Airway Bacteria and Inflammation in People with Cystic Fibrosis and Chronic Lung Infections","volume":"195","author":"Hisert","year":"2017","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1038\/s41525-017-0015-6","article-title":"Phenotypic profiling of CFTR modulators in patient-derived respiratory epithelia","volume":"2","author":"Ahmadi","year":"2017","journal-title":"NPJ Genom. Med."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"388","DOI":"10.1016\/j.jcf.2017.03.003","article-title":"Real-life initiation of lumacaftor\/ivacaftor combination in adults with cystic fibrosis homozygous for the Phe508del CFTR mutation and severe lung disease","volume":"16","author":"Hubert","year":"2017","journal-title":"J. Cyst. Fibros."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1662","DOI":"10.1513\/AnnalsATS.201701-058OC","article-title":"An observational study of outcomes and tolerances in patients with cystic fibrosis initiated on lumacaftor\/ivacaftor","volume":"14","author":"Jennings","year":"2017","journal-title":"Ann. Am. Thorac. Soc."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"368","DOI":"10.1016\/j.jcf.2018.12.011","article-title":"Predictive factors for lumacaftor\/ivacaftor clinical response","volume":"18","author":"Masson","year":"2019","journal-title":"J. Cyst. Fibros."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"e86183","DOI":"10.1172\/jci.insight.86183","article-title":"Acute administration of ivacaftor to people with cystic fibrosis and a G551D-CFTR mutation reveals smooth muscle abnormalities","volume":"1","author":"Adam","year":"2016","journal-title":"JCI Insight"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"900","DOI":"10.1002\/ppul.23712","article-title":"CFTR-dependent chloride efflux in cystic fibrosis mononuclear cells is increased by ivacaftor therapy","volume":"52","author":"Guerra","year":"2017","journal-title":"Pediatr. Pulmonol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"00318","DOI":"10.1183\/23120541.00318-2019","article-title":"Ivacaftor decreases monocyte sensitivity to interferon-gamma in people with cystic fibrosis","volume":"6","author":"Hisert","year":"2020","journal-title":"ERJ Open Res."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"594","DOI":"10.1165\/rcmb.2015-0322LE","article-title":"Ivacaftor-induced proteomic changes suggest monocyte defects may contribute to the pathogenesis of cystic fibrosis","volume":"54","author":"Hisert","year":"2016","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"643","DOI":"10.1165\/rcmb.2019-0032OC","article-title":"Transcriptomic responses to ivacaftor and prediction of ivacaftor clinical responsiveness","volume":"61","author":"Sun","year":"2019","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"3088","DOI":"10.1016\/j.bbagen.2014.07.010","article-title":"Electrophysiological evaluation of cystic fibrosis conductance transmembrane regulator (CFTR) expression in human monocytes","volume":"1840","author":"Ettorre","year":"2014","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"3757","DOI":"10.12998\/wjcc.v7.i22.3757","article-title":"Cystic fibrosis transmembrane conductance regulator functional evaluations in a G542X+\/\u2212 IVS8Tn:T7\/9 patient with acute recurrent pancreatitis","volume":"7","author":"Caldrer","year":"2019","journal-title":"World J. Clin. Cases"},{"key":"ref_79","doi-asserted-by":"crossref","unstructured":"Caldrer, S., Verze, G., Johansson, J., Sorio, C., Angiari, C., Buffelli, M., Assael, B.M., and Melotti, P. (2014). Challenging the diagnosis of cystic fibrosis in a patient carrying the 186-8T\/C allelic variant in the CF transmembrane conductance regulator gene. BMC Pulm. Med., 14.","DOI":"10.1186\/1471-2466-14-44"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"821","DOI":"10.1016\/j.jcf.2012.12.014","article-title":"Impaired CFTR function in mild cystic fibrosis associated with the S977F\/T5TG12complex allele in trans with F508del mutation","volume":"12","author":"Sorio","year":"2013","journal-title":"J. Cyst. Fibros."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"1413","DOI":"10.1189\/jlb.4A0316-130RR","article-title":"CFTR targeting during activation of human neutrophils","volume":"100","author":"Ng","year":"2016","journal-title":"J. Leukoc. Biol."}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/10\/12\/3380\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:38:23Z","timestamp":1760168303000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/10\/12\/3380"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,12,1]]},"references-count":81,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2021,12]]}},"alternative-id":["cells10123380"],"URL":"https:\/\/doi.org\/10.3390\/cells10123380","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,12,1]]}}}