T helper type 17-related cytokine expression is increased in the bronchial mucosa of stable chronic obstructive pulmonary disease patients

• Published in: Clinical and experimental immunology 2009-08, Vol.157 (2), p.316-324
• Main Authors: Di Stefano, A, Caramori, G, Gnemmi, I, Contoli, M, Vicari, C, Capelli, A, Magno, F, D'Anna, S.E, Zanini, A, Brun, P, Casolari, P, Chung, K.F, Barnes, P.J, Papi, A, Adcock, I, Balbi, B
• Format: Article
• Language: English
• Subjects: Aged; Analysis of Variance; Analytical, structural and metabolic biochemistry; autoimmunity; Biological and medical sciences; Biopsy; Bronchi - immunology; bronchial biopsies; Case-Control Studies; CD4 antigen; CD8 antigen; Chronic obstructive pulmonary disease; Chronic obstructive pulmonary disease, asthma; DNA Primers - genetics; emphysema; Endothelial cells; Epithelium; Female; Fundamental and applied biological sciences. Psychology; Gene expression; Helper cells; Humans; Immunohistochemistry; Inflammation; Interleukin 21; Interleukin 22; Interleukin 23; Interleukin-17 - immunology; Interleukin-23 - genetics; Interleukin-23 - immunology; Interleukins - genetics; Interleukins - immunology; Lymphocytes T; Male; Medical sciences; Middle Aged; Mucosa; Mucous Membrane - immunology; neutrophils; Nuclear Receptor Subfamily 1, Group F, Member 3; Orphan receptors; pathological processes and conditions; pathology; Pneumology; Polymerase Chain Reaction; Pulmonary Disease, Chronic Obstructive - immunology; Receptors, Retinoic Acid - genetics; Receptors, Retinoic Acid - immunology; Receptors, Thyroid Hormone - genetics; Receptors, Thyroid Hormone - immunology; Respiratory Function Tests; RNA, Messenger - analysis; Smoking - adverse effects; Statistics, Nonparametric; T-Lymphocytes, Helper-Inducer - immunology; Translational Studies
• ISSN: 0009-9104; 1365-2249
• DOI: 10.1111/j.1365-2249.2009.03965.x

There are increased numbers of activated T lymphocytes in the bronchial mucosa of stable chronic obstructive pulmonary disease (COPD) patients. T helper type 17 (Th17) cells release interleukin (IL)-17 as their effector cytokine under the control of IL-22 and IL-23. Furthermore, Th17 numbers are increased in some chronic inflammatory conditions. To investigate the expression of interleukin (IL)-17A, IL-17F, IL-21, IL-22 and IL-23 and of retinoic orphan receptor RORC2, a marker of Th17 cells, in bronchial biopsies from patients with stable COPD of different severity compared with age-matched control subjects. The expression of IL-17A, IL-17F, IL-21, IL-22, IL-23 and RORC2 was measured in the bronchial mucosa using immunohistochemistry and/or quantitative polymerase chain reaction. The number of IL-22⁺ and IL-23⁺ immunoreactive cells is increased in the bronchial epithelium of stable COPD compared with control groups. In addition, the number of IL-17A⁺ and IL-22⁺ immunoreactive cells is increased in the bronchial submucosa of stable COPD compared with control non-smokers. In all smokers, with and without disease, and in patients with COPD alone, the number of IL-22⁺ cells correlated significantly with the number of both CD4⁺ and CD8⁺ cells in the bronchial mucosa. RORC2 mRNA expression in the bronchial mucosa was not significantly different between smokers with normal lung function and COPD. Further, we report that endothelial cells express high levels of IL-17A and IL-22. Increased expression of the Th17-related cytokines IL-17A, IL-22 and IL-23 in COPD patients may reflect their involvement, and that of specific IL-17-producing cells, in driving the chronic inflammation seen in COPD.