Immune Netw.  2010 Aug;10(4):109-114. 10.4110/in.2010.10.4.109.

Role of Th17 Cell and Autoimmunity in Chronic Obstructive Pulmonary Disease

• Hong SC
• Lee SH

• KMID: 2150668
• DOI: http://doi.org/10.4110/in.2010.10.4.109

Abstract

The molecular mechanisms involved in the pathogenesis of chronic obstructive pulmonary disease (COPD) are poorly defined. Accumulating evidences indicate that chronic inflammatory responses and adaptive immunity play important roles in the development and progression of the disease. Recently, it has been shown that IL-17 producing CD4 T cells, named Th17 cells, which have been implicated in the pathogenesis of several inflammatory and autoimmune diseases, are involved in airway inflammation and COPD. In addition, we and others suggest that autoimmunity may play a critical role in the pathogenesis of COPD. Here, we will review the current understanding of roles of Th17 cells and autoimmune responses in COPD.

Keyword

COPD; Inflammation; Th17 cells; Autoimmunity

MeSH Terms

Adaptive Immunity
Autoimmune Diseases
Autoimmunity
Inflammation
Interleukin-17
Pulmonary Disease, Chronic Obstructive
T-Lymphocytes
Th17 Cells
Interleukin-17

Reference

1. Hogg JC, Timens W. The pathology of chronic obstructive pulmonary disease. Annu Rev Pathol. 2009. 4:435–459.

2. Mathers CD, Loncar D. Projections of global mortality and burden of disease from 2002 to 2030. PLoS Med. 2006. 3:e442.

3. Fletcher C, Peto R. The natural history of chronic airflow obstruction. Br Med J. 1977. 1:1645–1648.

4. Ind PW. COPD disease progression and airway inflammation: uncoupled by smoking cessation. Eur Respir J. 2005. 26:764–766.

5. Simmons MS, Connett JE, Nides MA, Lindgren PG, Kleerup EC, Murray RP, Bjornson WM, Tashkin DP. Smoking reduction and the rate of decline in FEV(1): results from the Lung Health Study. Eur Respir J. 2005. 25:1011–1017.

6. Chung KF, Adcock IM. Multifaceted mechanisms in COPD: inflammation, immunity, and tissue repair and destruction. Eur Respir J. 2008. 31:1334–1356.

7. Sharafkhaneh A, Hanania NA, Kim V. Pathogenesis of emphysema: from the bench to the bedside. Proc Am Thorac Soc. 2008. 5:475–477.

8. Taraseviciene-Stewart L, Voelkel NF. Molecular pathogenesis of emphysema. J Clin Invest. 2008. 118:394–402.

9. Tuder RM, Yoshida T, Arap W, Pasqualini R, Petrache I. State of the art. Cellular and molecular mechanisms of alveolar destruction in emphysema: an evolutionary perspective. Proc Am Thorac Soc. 2006. 3:503–510.

10. Motz GT, Eppert BL, Sun G, Wesselkamper SC, Linke MJ, Deka R, Borchers MT. Persistence of lung CD8 T cell oligoclonal expansions upon smoking cessation in a mouse model of cigarette smoke-induced emphysema. J Immunol. 2008. 181:8036–8043.

11. Motz GT, Eppert BL, Wesselkamper SC, Flury JL, Borchers MT. Chronic cigarette smoke exposure generates pathogenic T cells capable of driving COPD-like disease in Rag2-/- mice. Am J Respir Crit Care Med. 2010. 181:1223–1233.

12. Sullivan AK, Simonian PL, Falta MT, Mitchell JD, Cosgrove GP, Brown KK, Kotzin BL, Voelkel NF, Fontenot AP. Oligoclonal CD4+ T cells in the lungs of patients with severe emphysema. Am J Respir Crit Care Med. 2005. 172:590–596.

13. Lee SH, Goswami S, Grudo A, Song LZ, Bandi V, Goodnight-White S, Green L, Hacken-Bitar J, Huh J, Bakaeen F, Coxson HO, Cogswell S, Storness-Bliss C, Corry DB, Kheradmand F. Antielastin autoimmunity in tobacco smoking-induced emphysema. Nat Med. 2007. 13:567–569.

14. Hogg JC, Chu F, Utokaparch S, Woods R, Elliott WM, Buzatu L, Cherniack RM, Rogers RM, Sciurba FC, Coxson HO, Paré PD. The nature of small-airway obstruction in chronic obstructive pulmonary disease. N Engl J Med. 2004. 350:2645–2653.

15. Baraldo S, Turato G, Badin C, Bazzan E, Beghé B, Zuin R, Calabrese F, Casoni G, Maestrelli P, Papi A, Fabbri LM, Saetta M. Neutrophilic infiltration within the airway smooth muscle in patients with COPD. Thorax. 2004. 59:308–312.

16. Keatings VM, Collins PD, Scott DM, Barnes PJ. Differences in interleukin-8 and tumor necrosis factor-alpha in induced sputum from patients with chronic obstructive pulmonary disease or asthma. Am J Respir Crit Care Med. 1996. 153:530–534.

17. Traves SL, Culpitt SV, Russell RE, Barnes PJ, Donnelly LE. Increased levels of the chemokines GROalpha and MCP-1 in sputum samples from patients with COPD. Thorax. 2002. 57:590–595.

18. Shapiro SD, Goldstein NM, Houghton AM, Kobayashi DK, Kelley D, Belaaouaj A. Neutrophil elastase contributes to cigarette smoke-induced emphysema in mice. Am J Pathol. 2003. 163:2329–2335.

19. Voynow JA, Young LR, Wang Y, Horger T, Rose MC, Fischer BM. Neutrophil elastase increases MUC5AC mRNA and protein expression in respiratory epithelial cells. Am J Physiol. 1999. 276:L835–L843.

20. Barnes PJ. Alveolar macrophages as orchestrators of COPD. COPD. 2004. 1:59–70.

21. Churg A, Wright JL. Proteases and emphysema. Curr Opin Pulm Med. 2005. 11:153–159.

22. Russell RE, Thorley A, Culpitt SV, Dodd S, Donnelly LE, Demattos C, Fitzgerald M, Barnes PJ. Alveolar macrophage-mediated elastolysis: roles of matrix metalloproteinases, cysteine, and serine proteases. Am J Physiol Lung Cell Mol Physiol. 2002. 283:L867–L873.

23. Finlay GA, Russell KJ, McMahon KJ, D'arcy EM, Masterson JB, FitzGerald MX, O'Connor CM. Elevated levels of matrix metalloproteinases in bronchoalveolar lavage fluid of emphysematous patients. Thorax. 1997. 52:502–506.

24. Hautamaki RD, Kobayashi DK, Senior RM, Shapiro SD. Requirement for macrophage elastase for cigarette smoke-induced emphysema in mice. Science. 1997. 277:2002–2004.

25. Grumelli S, Corry DB, Song LZ, Song L, Green L, Huh J, Hacken J, Espada R, Bag R, Lewis DE, Kheradmand F. An immune basis for lung parenchymal destruction in chronic obstructive pulmonary disease and emphysema. PLoS Med. 2004. 1:e8.

26. Fujita M, Shannon JM, Irvin CG, Fagan KA, Cool C, Augustin A, Mason RJ. Overexpression of tumor necrosis factor-alpha produces an increase in lung volumes and pulmonary hypertension. Am J Physiol Lung Cell Mol Physiol. 2001. 280:L39–L49.

27. Aaron SD, Angel JB, Lunau M, Wright K, Fex C, Le Saux N, Dales RE. Granulocyte inflammatory markers and airway infection during acute exacerbation of chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2001. 163:349–355.

28. Dentener MA, Creutzberg EC, Pennings HJ, Rijkers GT, Mercken E, Wouters EF. Effect of infliximab on local and systemic inflammation in chronic obstructive pulmonary disease: a pilot study. Respiration. 2008. 76:275–282.

29. Rennard SI, Fogarty C, Kelsen S, Long W, Ramsdell J, Allison J, Mahler D, Saadeh C, Siler T, Snell P, Korenblat P, Smith W, Kaye M, Mandel M, Andrews C, Prabhu R, Donohue JF, Watt R, Lo KH, Schlenker-Herceg R, Barnathan ES, Murray J. COPD Investigators. The safety and efficacy of infliximab in moderate to severe chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2007. 175:926–934.

30. Sapey E, Ahmad A, Bayley D, Newbold P, Snell N, Rugman P, Stockley RA. Imbalances between interleukin-1 and tumor necrosis factor agonists and antagonists in stable COPD. J Clin Immunol. 2009. 29:508–516.

31. Bhowmik A, Seemungal TA, Sapsford RJ, Wedzicha JA. Relation of sputum inflammatory markers to symptoms and lung function changes in COPD exacerbations. Thorax. 2000. 55:114–120.

32. Calabrese F, Baraldo S, Bazzan E, Lunardi F, Rea F, Maestrelli P, Turato G, Lokar-Oliani K, Papi A, Zuin R, Sfriso P, Balestro E, Dinarello CA, Saetta M. IL-32, a novel proinflammatory cytokine in chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2008. 178:894–901.

33. Miossec P, Korn T, Kuchroo VK. Interleukin-17 and type 17 helper T cells. N Engl J Med. 2009. 361:888–898.

34. Louten J, Boniface K, de Waal Malefyt R. Development and function of TH17 cells in health and disease. J Allergy Clin Immunol. 2009. 123:1004–1011.

35. Jones CE, Chan K. Interleukin-17 stimulates the expression of interleukin-8, growth-related oncogene-alpha, and granulocyte-colony-stimulating factor by human airway epithelial cells. Am J Respir Cell Mol Biol. 2002. 26:748–753.

36. Kao CY, Huang F, Chen Y, Thai P, Wachi S, Kim C, Tam L, Wu R. Up-regulation of CC chemokine ligand 20 expression in human airway epithelium by IL-17 through a JAK-independent but MEK/NF-kappaB-dependent signaling pathway. J Immunol. 2005. 175:6676–6685.

37. Chen Y, Thai P, Zhao YH, Ho YS, DeSouza MM, Wu R. Stimulation of airway mucin gene expression by interleukin (IL)-17 through IL-6 paracrine/autocrine loop. J Biol Chem. 2003. 278:17036–17043.

38. 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. 6:1133–1141.

39. Harrison OJ, Foley J, Bolognese BJ, Long E 3rd, Podolin PL, Walsh PT. Airway infiltration of CD4+ CCR6+ Th17 type cells associated with chronic cigarette smoke induced airspace enlargement. Immunol Lett. 2008. 121:13–21.

40. Barczyk A, Pierzchala W, Sozañska E. Interleukin-17 in sputum correlates with airway hyperresponsiveness to methacholine. Respir Med. 2003. 97:726–733.

41. Ikeuchi H, Kuroiwa T, Hiramatsu N, Kaneko Y, Hiromura K, Ueki K, Nojima Y. Expression of interleukin-22 in rheumatoid arthritis: potential role as a proinflammatory cytokine. Arthritis Rheum. 2005. 52:1037–1046.

42. Wolk K, Witte E, Warszawska K, Schulze-Tanzil G, Witte K, Philipp S, Kunz S, Döcke WD, Asadullah K, Volk HD, Sterry W, Sabat R. The Th17 cytokine IL-22 induces IL-20 production in keratinocytes: a novel immunological cascade with potential relevance in psoriasis. Eur J Immunol. 2009. 39:3570–3581.

43. Aujla SJ, Chan YR, Zheng M, Fei M, Askew DJ, Pociask DA, Reinhart TA, McAllister F, Edeal J, Gaus K, Husain S, Kreindler JL, Dubin PJ, Pilewski JM, Myerburg MM, Mason CA, Iwakura Y, Kolls JK. IL-22 mediates mucosal host defense against Gram-negative bacterial pneumonia. Nat Med. 2008. 14:275–281.

44. 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. 157:316–324.

45. Sonnenberg GF, Nair MG, Kirn TJ, Zaph C, Fouser LA, Artis D. Pathological versus protective functions of IL-22 in airway inflammation are regulated by IL-17A. J Exp Med. 2010. 207:1293–1305.

46. Cua DJ, Sherlock J, Chen Y, Murphy CA, Joyce B, Seymour B, Lucian L, To W, Kwan S, Churakova T, Zurawski S, Wiekowski M, Lira SA, Gorman D, Kastelein RA, Sedgwick JD. Interleukin-23 rather than interleukin-12 is the critical cytokine for autoimmune inflammation of the brain. Nature. 2003. 421:744–748.

47. Murphy CA, Langrish CL, Chen Y, Blumenschein W, McClanahan T, Kastelein RA, Sedgwick JD, Cua DJ. Divergent pro- and antiinflammatory roles for IL-23 and IL-12 in joint autoimmune inflammation. J Exp Med. 2003. 198:1951–1957.

48. Langrish CL, Chen Y, Blumenschein WM, Mattson J, Basham B, Sedgwick JD, McClanahan T, Kastelein RA, Cua DJ. IL-23 drives a pathogenic T cell population that induces autoimmune inflammation. J Exp Med. 2005. 201:233–240.

49. Voelkel N, Taraseviciene-Stewart L. Emphysema: an autoimmune vascular disease? Proc Am Thorac Soc. 2005. 2:23–25.

50. Agustí A, MacNee W, Donaldson K, Cosio M. Hypothesis: does COPD have an autoimmune component? Thorax. 2003. 58:832–834.

51. Shan M, Cheng HF, Song LZ, Roberts L, Green L, Hacken-Bitar J, Huh J, Bakaeen F, Coxson HO, Storness-Bliss C, Ramchandani M, Lee SH, Corry DB, Kheradmand F. Lung myeloid dendritic cells coordinately induce TH1 and TH17 responses in human emphysema. Science Translational Medicine. 2009. 1:4ra10.

52. Cottin V, Fabien N, Khouatra C, Moreira A, Cordier JF. Anti-elastin autoantibodies are not present in combined pulmonary fibrosis and emphysema. Eur Respir J. 2009. 33:219–221.

53. Greene CM, Low TB, O'Neill SJ, McElvaney NG. Anti-proline-glycine-proline or antielastin autoantibodies are not evident in chronic inflammatory lung disease. Am J Respir Crit Care Med. 2010. 181:31–35.