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

Publisher: European Respiratory Society Country of Publication: England NLM ID: 8803460 Publication Model: Electronic-Print Cited Medium: Internet ISSN: 1399-3003 (Electronic) Linking ISSN: 09031936 NLM ISO Abbreviation: Eur Respir J Subsets: MEDLINE

Publication: Sheffield, United Kingdom : European Respiratory Society
Original Publication: Copenhagen : Published jointly by the Society and Munksgaard, 1988-

Emphysema/*etiology ; Interleukins/*physiology ; Pulmonary Disease, Chronic Obstructive/*pathology ; Receptors, Interleukin/*physiology; Airway Remodeling ; Airway Resistance ; Animals ; Emphysema/pathology ; Female ; Humans ; Immunity, Innate ; Lymphocytes/metabolism ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Pulmonary Disease, Chronic Obstructive/chemically induced ; Pulmonary Disease, Chronic Obstructive/metabolism ; Smoke/adverse effects ; Tobacco Products ; Interleukin-22

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.
Competing Interests: Conflict of interest: M.R. Starkey has nothing to disclose. Conflict of interest: M.W. Plank is a full-time employee of GlaxoSmithKline. Conflict of interest: P. Casolari has nothing to disclose. Conflict of interest: A. Papi reports board membership, consultancy, payment for lectures, grants for research and travel expenses reimbursement from Chiesi, AstraZeneca, GlaxoSmithKline, Boehringer Ingelheim, Mundipharma and TEVA, payment for lectures and travel expenses reimbursement from Menarini, Novartis, Zambon and Sanofi, outside the submitted work. Conflict of interest: S. Pavlidis has nothing to disclose. Conflict of interest: Y Guo has nothing to disclose. Conflict of interest: G.J.M. Cameron has nothing to disclose. Conflict of interest: T.J. Haw has nothing to disclose. Conflict of interest: A. Tam has nothing to disclose. Conflict of interest: M. Obeidat has nothing to disclose. Conflict of interest: C. Donovan has nothing to disclose. Conflict of interest: N.G. Hansbro has nothing to disclose. Conflict of interest: D.H. Nguyen has nothing to disclose. Conflict of interest: P.M. Nair has nothing to disclose. Conflict of interest: R.Y. Kim has nothing to disclose. Conflict of interest: J.C. Horvat has nothing to disclose. Conflict of interest: G.E. Kaiko has nothing to disclose. Conflict of interest: S.K. Durum has nothing to disclose. Conflict of interest: P.A. Wark has nothing to disclose. Conflict of interest: D.D. Sin reports grants from Merck, personal fees for advisory board work from Sanofi-Aventis and Regeneron, grants and personal fees from Boehringer Ingelheim, grants and personal fees for lecturing and advisory board work from AstraZeneca, personal fees for lecturing and advisory board work from Novartis, outside the submitted work. Conflict of interest: G. Caramori has nothing to disclose. Conflict of interest: I.M. Adcock has nothing to disclose. Conflict of interest: P.S. Foster has nothing to disclose. Conflict of interest: P.M. Hansbro reports funding/consultancies from Pharmaxis, AstraZeneca, Sanofi, Pharmakea, Ausbio, and Allakos outside the submitted work.
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Am J Respir Crit Care Med. 2007 Sep 15;176(6):556-64. (PMID: 17600276)
JCI Insight. 2017 Apr 6;2(7):e90443. (PMID: 28405612)
Sci Rep. 2019 Mar 4;9(1):3353. (PMID: 30833624)
Lancet. 2012 Dec 15;380(9859):2095-128. (PMID: 23245604)
J Allergy Clin Immunol. 2013 Mar;131(3):752-62. (PMID: 23380220)
J Biol Chem. 2014 Jun 27;289(26):18214-27. (PMID: 24821729)
Proc Natl Acad Sci U S A. 2001 Aug 14;98(17):9511-6. (PMID: 11481447)
J Immunol. 2017 Mar 1;198(5):2182-2190. (PMID: 28100680)
Am J Physiol Lung Cell Mol Physiol. 2018 Feb 1;314(2):L298-L317. (PMID: 29025711)
EBioMedicine. 2015 Sep 26;2(11):1686-96. (PMID: 26870795)
Eur Respir J. 2015 Sep;46(3):771-82. (PMID: 26250498)
Am J Respir Crit Care Med. 2017 Aug 1;196(3):283-297. (PMID: 28252317)
Acta Pharmacol Sin. 2014 Nov;35(11):1393-401. (PMID: 25345745)
Mucosal Immunol. 2014 May;7(3):478-88. (PMID: 24045576)
JCI Insight. 2018 Feb 8;3(3):. (PMID: 29415878)
J Allergy Clin Immunol. 2017 Feb;139(2):519-532. (PMID: 27448447)
Am J Respir Crit Care Med. 2015 May 1;191(9):1012-23. (PMID: 25751541)
Annu Rev Immunol. 2015;33:747-85. (PMID: 25706098)
Expert Rev Clin Immunol. 2013 Nov;9(11):1055-68. (PMID: 24168412)
J Allergy Clin Immunol. 2010 Mar;125(3):617-25, 625.e1-625.e6. (PMID: 20122715)
Lancet Respir Med. 2019 Oct;7(10):907-920. (PMID: 30975495)
Allergy. 2017 Dec;72(12):1891-1903. (PMID: 28543283)
Mucosal Immunol. 2013 May;6(3):569-79. (PMID: 23131786)
Expert Opin Drug Discov. 2014 Jun;9(6):629-45. (PMID: 24754714)
Mucosal Immunol. 2017 Jan;10(1):139-149. (PMID: 27143304)
Thorax. 2015 May;70(5):458-67. (PMID: 25746630)
Genome Med. 2012 Aug 31;4(8):67. (PMID: 22937864)
J Mol Med (Berl). 2007 Jan;85(1):39-53. (PMID: 17115125)
PLoS One. 2016 Jan 04;11(1):e0145961. (PMID: 26727464)
Nat Rev Microbiol. 2017 Jan;15(1):55-63. (PMID: 27694885)
Mucosal Immunol. 2012 Jan;5(1):7-18. (PMID: 22089028)
Respirology. 2017 Jan;22(1):21-32. (PMID: 27731525)
Mucosal Immunol. 2016 Jul;9(4):859-72. (PMID: 26555706)
Cell Death Dis. 2017 Jul 20;8(7):e2937. (PMID: 28726774)
Cancer Res. 2006 Nov 15;66(22):10729-40. (PMID: 17108109)
Am J Physiol Lung Cell Mol Physiol. 2005 Aug;289(2):L322-8. (PMID: 15833762)
Eur Respir J. 2017 Oct 12;50(4):. (PMID: 29025886)
JCI Insight. 2016 Jun 16;1(9):. (PMID: 27398409)
Elife. 2017 Feb 14;6:. (PMID: 28195529)
Am J Pathol. 2013 Apr;182(4):1286-96. (PMID: 23490254)
Exp Lung Res. 2007 Dec;33(10):507-18. (PMID: 18075825)
Am J Respir Crit Care Med. 2017 Mar 1;195(5):557-582. (PMID: 28128970)
J Allergy Clin Immunol. 2013 Mar;131(3):636-45. (PMID: 23360759)
Mucosal Immunol. 2014 May;7(3):568-78. (PMID: 24172846)
Clin Transl Immunology. 2017 Mar 10;6(3):e133. (PMID: 28435675)
Sci Transl Med. 2012 Jan 18;4(117):117ra9. (PMID: 22261033)

United Kingdom WT_ Wellcome Trust; Z01 BC009287 United States ImNIH Intramural NIH HHS

0 (Interleukins)
0 (Receptors, Interleukin)
0 (Smoke)
0 (interleukin-22 receptor)

Date Created: 20190615 Date Completed: 20200915 Latest Revision: 20231213

20240628

PMC8132110

10.1183/13993003.00174-2018

31196943