IL-22 and its receptors are increased in human and experimental COPD and contribute to pathogenesis

Malcolm R. Starkey, Maximilian W. Plank, Paolo Casolari, Alberto Papi, Stelios Pavlidis, Yike Guo, Guy J.M. Cameron, Tatt Jhong Haw, Anthony Tam, Ma'en Obiedat, Chantal Donovan, Nicole G. Hansbro, Duc H. Nguyen, Prema Mono Nair, Richard Y. Kim, Jay C. Horvat, Gerard E. Kaiko, Scott K. Durum, Peter A. Wark, Don D. SinGaetano Caramori, Ian M. Adcock, Paul S. Foster, Philip M. Hansbro

Research output: Contribution to journalArticleResearchpeer-review

8 Citations (Scopus)

Abstract

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 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.

Original languageEnglish
Article number1800174
Number of pages14
JournalThe European respiratory journal
Volume54
Issue number1
DOIs
Publication statusPublished - 1 Jul 2019
Externally publishedYes

Cite this

Starkey, M. R., Plank, M. W., Casolari, P., Papi, A., Pavlidis, S., Guo, Y., Cameron, G. J. M., Haw, T. J., Tam, A., Obiedat, M., Donovan, C., Hansbro, N. G., Nguyen, D. H., Nair, P. M., Kim, R. Y., Horvat, J. C., Kaiko, G. E., Durum, S. K., Wark, P. A., ... Hansbro, P. M. (2019). IL-22 and its receptors are increased in human and experimental COPD and contribute to pathogenesis. The European respiratory journal, 54(1), [1800174]. https://doi.org/10.1183/13993003.00174-2018