Respiratory Research | |
CD8 positive T cells express IL-17 in patients with chronic obstructive pulmonary disease | |
Qutayba Hamid3  David H Eidelman3  François Maltais1  Jean Bourbeau2  Nicholas Boulais3  Jessica Nadigel3  Ying Chang3  | |
[1] Respiratory Division, Laval University, 2325 rue de l'Université, Québec, QC, G1V0A6 Canada;Respiratory Division, Research Institute of McGill University Health Centre, 2155 Guy Street, Suite 900 Montreal, QC, H3H 2R9 Canada;Meakins-Christie Laboratories and Respiratory Division, Department of Medicine McGill University, 3626 rue St. Urbain, Montreal, QC, H2X 2P2 Canada | |
关键词: Tc17 cells; IL-17; Chronic Obstructive Pulmonary Disease; | |
Others : 796883 DOI : 10.1186/1465-9921-12-43 |
|
received in 2010-08-26, accepted in 2011-04-10, 发布年份 2011 | |
【 摘 要 】
Background
Chronic obstructive pulmonary disease (COPD) is a progressive and irreversible chronic inflammatory disease of the lung. The nature of the immune reaction in COPD raises the possibility that IL-17 and related cytokines may contribute to this disorder. This study analyzed the expression of IL-17A and IL-17F as well as the phenotype of cells producing them in bronchial biopsies from COPD patients.
Methods
Bronchoscopic biopsies of the airway were obtained from 16 COPD subjects (GOLD stage 1-4) and 15 control subjects. Paraffin sections were used for the investigation of IL-17A and IL-17F expression in the airways by immunohistochemistry, and frozen sections were used for the immunofluorescence double staining of IL-17A or IL-17F paired with CD4 or CD8. In order to confirm the expression of IL-17A and IL-17F at the mRNA level, a quantitative RT-PCR was performed on the total mRNA extracted from entire section or CD8 positive cells selected by laser capture microdissection.
Results
IL-17F immunoreactivity was significantly higher in the bronchial biopsies of COPD patients compared to control subjects (P < 0.0001). In the submucosa, the absolute number of both IL-17A and IL-17F positive cells was higher in COPD patients (P < 0.0001). After adjusting for the total number of cells in the submucosa, we still found that more cells were positive for both IL-17A (P < 0.0001) and IL-17F (P < 0.0001) in COPD patients compared to controls. The mRNA expression of IL-17A and IL-17F in airways of COPD patients was confirmed by RT-PCR. The expression of IL-17A and IL-17F was co-localized with not only CD4 but also CD8, which was further confirmed by RT-PCR on laser capture microdissection selected CD8 positive cells.
Conclusion
These findings support the notion that Th17 cytokines could play important roles in the pathogenesis of COPD, raising the possibility of using this mechanism as the basis for novel therapeutic approaches.
【 授权许可】
2011 Chang et al; licensee BioMed Central Ltd.
【 预 览 】
Files | Size | Format | View |
---|---|---|---|
20140706014618656.pdf | 7638KB | download | |
Figure 4. | 73KB | Image | download |
Figure 3. | 30KB | Image | download |
Figure 2. | 28KB | Image | download |
Figure 1. | 97KB | Image | download |
【 图 表 】
Figure 1.
Figure 2.
Figure 3.
Figure 4.
【 参考文献 】
- [1]Pauwels RA, Rabe KF: Burden and clinical features of chronic obstructive pulmonary disease (COPD). Lancet 2004, 364(9434):613-620.
- [2]Cosio MG, Saetta M, Agusti A: Immunologic aspects of chronic obstructive pulmonary disease. N Engl J Med 2009, 360(23):2445-2454.
- [3]Roth M: Pathogenesis of COPD. Part III. Inflammation in COPD. Int J Tuberc Lung Dis 2008, 12(4):375-380.
- [4]Cosio MG, Majo J: Inflammation of the airways and lung parenchyma in COPD: role of T cells. Chest 2002, 121(5 Suppl):160S-165S.
- [5]Agusti A, MacNee W, Donaldson K, Cosio M: Hypothesis: does COPD have an autoimmune component? Thorax 2003, 58(10):832-834.
- [6]Kolls JK, Linden A: Interleukin-17 family members and inflammation. Immunity 2004, 21(4):467-476.
- [7]Liang SC, Long AJ, Bennett F, Whitters MJ, Karim R, Collins M, Goldman SJ, Dunussi-Joannopoulos K, Williams CM, Wright JF, Fouser LA: An IL-17F/A heterodimer protein is produced by mouse Th17 cells and induces airway neutrophil recruitment. J Immunol 2007, 179(11):7791-7799.
- [8]Wright JF, Guo Y, Quazi A, Luxenberg DP, Bennett F, Ross JF, Qiu Y, Whitters MJ, Tomkinson KN, Dunussi-Joannopoulos K, Carreno BM, Collins M, Wolfman NM: Identification of an interleukin 17F/17A heterodimer in activated human CD4+ T cells. J Biol Chem 2007, 282(18):13447-13455.
- [9]Huber M, Heink S, Grothe H, Guralnik A, Reinhard K, Elflein K, Hunig T, Mittrucker HW, Brustle A, Kamradt T, Lohoff M: A Th17-like developmental process leads to CD8(+) Tc17 cells with reduced cytotoxic activity. Eur J Immunol 2009, 39(7):1716-1725.
- [10]Kramer JM, Gaffen SL: Interleukin-17: a new paradigm in inflammation, autoimmunity, and therapy. J Periodontol 2007, 78(6):1083-1093.
- [11]Miossec P, Korn T, Kuchroo VK: Interleukin-17 and type 17 helper T cells. N Engl J Med 2009, 361(9):888-898.
- [12]Fujisawa T, Velichko S, Thai P, Hung LY, Huang F, Wu R: Regulation of airway MUC5AC expression by IL-1beta and IL-17A; the NF-kappaB paradigm. J Immunol 2009, 183(10):6236-6243.
- [13]Park H, Li Z, Yang XO, Chang SH, Nurieva R, Wang YH, Wang Y, Hood L, Zhu Z, Tian Q, Dong C: A distinct lineage of CD4 T cells regulates tissue inflammation by producing interleukin 17. Nat Immunol 2005, 6(11):1133-1141.
- [14]Hizawa N, Kawaguchi M, Huang SK, Nishimura M: Role of interleukin-17F in chronic inflammatory and allergic lung disease. Clin Exp Allergy 2006, 36(9):1109-1114.
- [15]McKinley L, Alcorn JF, Peterson A, Dupont RB, Kapadia S, Logar A, Henry A, Irvin CG, Piganelli JD, Ray A, Kolls JK: TH17 cells mediate steroid-resistant airway inflammation and airway hyperresponsiveness in mice. J Immunol 2008, 181(6):4089-4097.
- [16]Hattotuwa KL, Gizycki MJ, Ansari TW, Jeffery PK, Barnes NC: The effects of inhaled fluticasone on airway inflammation in chronic obstructive pulmonary disease: a double-blind, placebo-controlled biopsy study. Am J Respir Crit Care Med 2002, 165(12):1592-1596.
- [17]Al-Ramli W, Prefontaine D, Chouiali F, Martin JG, Olivenstein R, Lemiere C, Hamid Q: T(H)17-associated cytokines (IL-17A and IL-17F) in severe asthma. J Allergy Clin Immunol 2009, 123(5):1185-1187.
- [18]Hodge G, Nairn J, Holmes M, Reynolds PN, Hodge S: Increased intracellular T helper 1 proinflammatory cytokine production in peripheral blood, bronchoalveolar lavage and intraepithelial T cells of COPD subjects. Clin Exp Immunol 2007, 150(1):22-29.
- [19]Lane N, Robins RA, Corne J, Fairclough L: Regulation in chronic obstructive pulmonary disease: the role of regulatory T-cells and Th17 cells. Clin Sci (Lond) 119(2):75-86.
- [20]Larsson K: Aspects on pathophysiological mechanisms in COPD. J Intern Med 2007, 262(3):311-340.
- [21]Prause O, Laan M, Lotvall J, Linden A: Pharmacological modulation of interleukin-17-induced GCP-2-, GRO-alpha- and interleukin-8 release in human bronchial epithelial cells. Eur J Pharmacol 2003, 462(1-3):193-198.
- [22]Wang JH, Devalia JL, Xia C, Sapsford RJ, Davies RJ: Expression of RANTES by human bronchial epithelial cells in vitro and in vivo and the effect of corticosteroids. Am J Respir Cell Mol Biol 1996, 14(1):27-35.
- [23]Suzuki S, Kokubu F, Kawaguchi M, Homma T, Odaka M, Watanabe S, Ieki K, Matsukura S, Kurokawa M, Takeuchi H, Sasaki Y, Huang SK, Adachi M, Ota H: Expression of interleukin-17F in a mouse model of allergic asthma. Int Arch Allergy Immunol 2007, 143(Suppl 1):89-94.
- [24]Yang XO, Chang SH, Park H, Nurieva R, Shah B, Acero L, Wang YH, Schluns KS, Broaddus RR, Zhu Z, Dong C: Regulation of inflammatory responses by IL-17F. J Exp Med 2008, 205(5):1063-1075.
- [25]Di Stefano A, Caramori G, Gnemmi I, Contoli M, Vicari C, Capelli A, Magno F, D'Anna SE, Zanini A, Brun P, Casolari P, Chung KF, Barnes PJ, Papi A, Adcock I, Balbi B: T helper type 17-related cytokine expression is increased in the bronchial mucosa of stable chronic obstructive pulmonary disease patients. Clin Exp Immunol 2009, 157(2):316-324.
- [26]Zhu X, Gadgil AS, Givelber R, George MP, Stoner MW, Sciurba FC, Duncan SR: Peripheral T cell functions correlate with the severity of chronic obstructive pulmonary disease. J Immunol 2009, 182(5):3270-3277.
- [27]Ortega C, Fernandez AS, Carrillo JM, Romero P, Molina IJ, Moreno JC, Santamaria M: IL-17-producing CD8+ T lymphocytes from psoriasis skin plaques are cytotoxic effector cells that secrete Th17-related cytokines. J Leukoc Biol 2009, 86(2):435-443.
- [28]Zhao Y, Balato A, Fishelevich R, Chapoval A, Mann DL, Gaspari AA: Th17/Tc17 infiltration and associated cytokine gene expression in elicitation phase of allergic contact dermatitis. Br J Dermatol 2009, 161(6):1301-1306.
- [29]Hamada H, Garcia-Hernandez Mde L, Reome JB, Misra SK, Strutt TM, McKinstry KK, Cooper AM, Swain SL, Dutton RW: Tc17, a unique subset of CD8 T cells that can protect against lethal influenza challenge. J Immunol 2009, 182(6):3469-3481.
- [30]Kader M, Bixler S, Piatak M, Lifson J, Mattapallil JJ: Anti-retroviral therapy fails to restore the severe Th-17: Tc-17 imbalance observed in peripheral blood during simian immunodeficiency virus infection. J Med Primatol 2009, 38(Suppl 1):32-38.
- [31]Nembrini C, Marsland BJ, Kopf M: IL-17-producing T cells in lung immunity and inflammation. J Allergy Clin Immunol 2009, 123(5):986-994. quiz 995-986
- [32]Kim V, Rogers TJ, Criner GJ: New concepts in the pathobiology of chronic obstructive pulmonary disease. Proc Am Thorac Soc 2008, 5(4):478-485.
- [33]Zhu J, Qiu Y, Valobra M, Qiu S, Majumdar S, Matin D, De Rose V, Jeffery PK: Plasma cells and IL-4 in chronic bronchitis and chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2007, 175(11):1125-1133.