PT - JOURNAL ARTICLE AU - Malcolm R. Starkey AU - Maximilian W. Plank AU - Paolo Casolari AU - Alberto Papi AU - Stelios Pavlidis AU - Yike Guo AU - Guy J.M. Cameron AU - Tatt Jhong Haw AU - Anthony Tam AU - Ma'en Obiedat AU - Chantal Donovan AU - Nicole G. Hansbro AU - Duc H. Nguyen AU - Prema Mono Nair AU - Richard Y. Kim AU - Jay C. Horvat AU - Gerard E. Kaiko AU - Scott K. Durum AU - Peter A. Wark AU - Don D. Sin AU - Gaetano Caramori AU - Ian M. Adcock AU - Paul S. Foster AU - Philip M. Hansbro TI - IL-22 and its receptors are increased in human and experimental COPD and contribute to pathogenesis AID - 10.1183/13993003.00174-2018 DP - 2019 Jan 01 TA - European Respiratory Journal PG - 1800174 4099 - http://erj.ersjournals.com/content/early/2019/04/25/13993003.00174-2018.short 4100 - http://erj.ersjournals.com/content/early/2019/04/25/13993003.00174-2018.full AB - Chronic Obstructive Pulmonary Disease (COPD) is the third leading cause of morbidity and death globally. The lack of effective treatments results from an incomplete understanding of the underlying mechanisms driving COPD pathogenesis.Interleukin (IL)-22 has been implicated in airway inflammation and is increased in COPD patients. However, its roles in the pathogenesis of COPD is poorly understood. Here, we investigated the role of IL-22 in human COPD and in cigarette smoke (CS)-induced experimental COPD.IL-22 and IL-22 receptor mRNA expression and protein levels were increased in COPD patients compared to healthy smoking or non-smoking controls. IL-22 and IL-22 receptor levels were increased in the lungs of mice with experimental COPD compared to controls and the cellular source of IL-22 included CD4+ T-helper cells, γδ T-cells, Natural Killer T-cells and group 3 innate lymphoid cells. CS-induced pulmonary neutrophils were reduced in IL-22-deficient (Il22−/−) mice. CS-induced airway remodelling and emphysema-like alveolar enlargement did not occur in Il22−/− mice. Il22−/− mice also had improved lung function in terms of airway resistance, total lung capacity, inspiratory capacity, forced vital capacity and compliance.These data highlight important roles for IL-22 and its receptors in human COPD and CS-induced experimental COPD.FootnotesThis manuscript has recently been accepted for publication in the European Respiratory Journal. It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article.Conflict of interest: Dr. Plank reports personal fees from GlaxoSmithKline, outside the submitted work.Conflict of interest: Dr. Casolari has nothing to disclose that is relevant to this manuscriptConflict of interest: Dr. Papi reports grants, personal fees, non-financial support and other from Chiesi, grants, personal fees, non-financial support and other from Astrazeneca, grants, personal fees, non-financial support and other from GlaxoSmithKline, grants, personal fees, non-financial support and other from Boehringer Ingelheim, personal fees and non-financial support from Menarini, personal fees and non-financial support from Novartis, personal fees and non-financial support from Zambon, personal fees and non-financial support from Sanofi, grants, personal fees, non-financial support and other from Mundipharma, grants, personal fees, non-financial support and other from TEVA, outside the submitted work.Conflict of interest: Dr. Pavlidis has nothing to disclose.Conflict of interest: Dr. Guo has nothing to disclose.Conflict of interest: Dr. Cameron has nothing to disclose.Conflict of interest: Dr. Haw has nothing to disclose.Conflict of interest: Dr. Tam has nothing to disclose.Conflict of interest: Dr. Obeidat has nothing to disclose.Conflict of interest: Dr. Donovan has nothing to disclose.Conflict of interest: Dr. Hansbro has nothing to disclose that is relevant to this manuscriptConflict of interest: Dr. Nguyen has nothing to disclose.Conflict of interest: Dr. Nair has nothing to disclose.Conflict of interest: Dr. Kim has nothing to disclose.Conflict of interest: Dr. Horvat has nothing to disclose.Conflict of interest: Dr. Kaiko has nothing to disclose.Conflict of interest: Dr. Durum has nothing to disclose.Conflict of interest: Dr. Wark has nothing to disclose.Conflict of interest: Dr. Sin reports grants from AstraZeneca, during the conduct of the study; grants from Merck, personal fees from Sanofi-Aventis, personal fees from Regeneron, grants and personal fees from Boehringer Ingelheim, grants and personal fees from AstraZeneca, personal fees from Novartis, outside the submitted work.Conflict of interest: Dr. Caramori has nothing to disclose that is relevant to this manuscriptConflict of interest: Dr. Adcock has nothing to disclose.Conflict of interest: Dr. Foster has nothing to disclose.Conflict of interest: Dr. Hansbro has nothing to disclose that is relevant to this manuscriptConflict of interest: Dr. Starkey has nothing to disclose.