Immune Netw.  2010 Feb;10(1):1-4. 10.4110/in.2010.10.1.1.

Role of IL-23 and Th17 Cells in Airway Inflammation in Asthma

• Nakajima H
• Hirose K

• KMID: 1456191
• DOI: http://doi.org/10.4110/in.2010.10.1.1

Abstract

Asthma is characterized by chronic airway inflammation with intense eosinophil and lymphocyte infiltration, mucus hyperproduction, and airway hyperresponsiveness. Accumulating evidence indicates that antigen-specific Th2 cells and their cytokines such as IL-4, IL-5, and IL-13 orchestrate these pathognomonic features of asthma. In addition, we and others have recently shown that IL-17-producing CD4+ T cells (Th17 cells) and IL-23, an IL-12-related cytokine that is essential for survival and functional maturation of Th17 cells, are involved in antigen-induced airway inflammation. In this review, our current understanding of the roles of IL-23 and Th17 cells in the pathogenesis of allergic airway inflammation will be summarized.

Keyword

Asthma; Eosinophils; Neutrophils; IL-17; IL-23; Th17 cells

MeSH Terms

Asthma
Cytokines
Eosinophils
Inflammation
Interleukin-13
Interleukin-17
Interleukin-23
Interleukin-4
Interleukin-5
Lymphocytes
Mucus
Neutrophils
T-Lymphocytes
Th17 Cells
Th2 Cells
Cytokines
Interleukin-13
Interleukin-17
Interleukin-23
Interleukin-4
Interleukin-5

Reference

1. Moseley TA, Haudenschild DR, Rose L, Reddi AH. Interleukin-17 family and IL-17 receptors. Cytokine Growth Factor Rev. 2003. 14:155–174.

2. Hymowitz SG, Filvaroff EH, Yin JP, Lee J, Cai L, Risser P, Maruoka M, Mao W, Foster J, Kelley RF, Pan G, Gurney AL, de Vos AM, Starovasnik MA. IL-17s adopt a cystine knot fold: structure and activity of a novel cytokine, IL-17F, and implications for receptor binding. EMBO J. 2001. 20:5332–5341.

3. McGeachy MJ, Cua DJ. Th17 cell differentiation: the long and winding road. Immunity. 2008. 28:445–453.

4. Korn T, Bettelli E, Oukka M, Kuchroo VK. IL-17 and Th17 cells. Annu Rev Immunol. 2009. 27:485–517.

5. Toy D, Kugler D, Wolfson M, Vanden Bos T, Gurgel J, Derry J, Tocker J, Peschon J. Cutting edge: interleukin 17 signals through a heteromeric receptor complex. J Immunol. 2006. 177:36–39.

6. Wright JF, Bennett F, Li B, Brooks J, Luxenberg DP, Whitters MJ, Tomkinson KN, Fitz LJ, Wolfman NM, Collins M, Dunussi-Joannopoulos K, Chatterjee-Kishore M, Carreno BM. The human IL-17F/IL-17A heterodimeric cytokine signals through the IL-17RA/IL-17RC receptor complex. J Immunol. 2008. 181:2799–2805.

7. Oppmann B, Lesley R, Blom B, Timans JC, Xu Y, Hunte B, Vega F, Yu N, Wang J, Singh K, Zonin F, Vaisberg E, Churakova T, Liu M, Gorman D, Wagner J, Zurawski S, Liu Y, Abrams JS, Moore KW, Rennick D, de Waal-Malefyt R, Hannum C, Bazan JF, Kastelein RA. Novel p19 protein engages IL-12p40 to form a cytokine, IL-23, with biological activities similar as well as distinct from IL-12. Immunity. 2000. 13:715–725.

8. 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.

9. McGeachy MJ, Bak-Jensen KS, Chen Y, Tato CM, Blumenschein W, McClanahan T, Cua DJ. TGF-beta and IL-6 drive the production of IL-17 and IL-10 by T cells and restrain T(H)17 cell-mediated pathology. Nat Immunol. 2007. 8:1390–1397.

10. Busse WW, Lemanske RF Jr. Asthma. N Engl J Med. 2001. 344:350–362.

11. Umetsu DT, McIntire JJ, Akbari O, Macaubas C, DeKruyff RH. Asthma: an epidemic of dysregulated immunity. Nat Immunol. 2002. 3:715–720.

12. Herrick CA, Bottomly K. To respond or not to respond: T cells in allergic asthma. Nat Rev Immunol. 2003. 3:405–412.

13. Hellings PW, Kasran A, Liu Z, Vandekerckhove P, Wuyts A, Overbergh L, Mathieu C, Ceuppens JL. Interleukin-17 orchestrates the granulocyte influx into airways after allergen inhalation in a mouse model of allergic asthma. Am J Respir Cell Mol Biol. 2003. 28:42–50.

14. Oda N, Canelos PB, Essayan DM, Plunkett BA, Myers AC, Huang SK. Interleukin-17F induces pulmonary neutrophilia and amplifies antigen-induced allergic response. Am J Respir Crit Care Med. 2005. 171:12–18.

15. Molet S, Hamid Q, Davoine F, Nutku E, Taha R, Pagé N, Olivenstein R, Elias J, Chakir J. IL-17 is increased in asthmatic airways and induces human bronchial fibroblasts to produce cytokines. J Allergy Clin Immunol. 2001. 108:430–438.

16. Jatakanon A, Uasuf C, Maziak W, Lim S, Chung KF, Barnes PJ. Neutrophilic inflammation in severe persistent asthma. Am J Respir Crit Care Med. 1999. 160:1532–1539.

17. Louis R, Lau LC, Bron AO, Roldaan AC, Radermecker M, Djukanović R. The relationship between airways inflammation and asthma severity. Am J Respir Crit Care Med. 2000. 161:9–16.

18. Iwakura Y, Nakae S, Saijo S, Ishigame H. The roles of IL-17A in inflammatory immune responses and host defense against pathogens. Immunol Rev. 2008. 266:55–79.

19. 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. 181:4089–4097.

20. Schnyder-Candrian S, Togbe D, Couillin I, Mercier I, Brombacher F, Quesniaux V, Fossiez F, Ryffel B, Schnyder B. Interleukin-17 is a negative regulator of established allergic asthma. J Exp Med. 2006. 203:2715–2725.

21. Wakashin H, Hirose K, Maezawa Y, Kagami S, Suto A, Watanabe N, Saito Y, Hatano M, Tokuhisa T, Iwakura Y, Puccetti P, Iwamoto I, Nakajima H. IL-23 and Th17 cells enhance Th2-cell-mediated eosinophilic airway inflammation in mice. Am J Respir Crit Care Med. 2008. 178:1023–1032.

22. Haworth O, Cernadas M, Yang R, Serhan CN, Levy BD. Resolvin E1 regulates interleukin 23, interferon-γ and lipoxin A4 to promote the resolution of allergic airway inflammation. Nat Immunol. 2008. 9:873–879.

23. Nakae S, Komiyama Y, Nambu A, Sudo K, Iwase M, Homma I, Sekikawa K, Asano M, Iwakura Y. Antigen-specific T cell sensitization is impaired in IL-17-deficient mice, causing suppression of allergic cellular and humoral responses. Immunity. 2002. 17:375–387.

24. Pichavant M, Goya S, Meyer EH, Johnston RA, Kim HY, Matangkasombut P, Zhu M, Iwakura Y, Savage PB, DeKruyff RH, Shore SA, Umetsu DT. Ozone exposure in a mouse model induces airway hyperreactivity that requires the presence of natural killer T cells and IL-17. J Exp Med. 2008. 205:385–393.

25. 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. 205:1063–1075.

26. Zheng Y, Danilenko DM, Valdez P, Kasman I, Eastham-Anderson J, Wu J, Ouyang W. Interleukin-22, a Th17 cytokine, mediates IL-23-induced dermal inflammation and acanthosis. Nature. 2007. 445:648–651.

27. Hoeck J, Woisetschläger M. STAT6 mediates eotaxin-1 expression in IL-4 or TNF-alpha-induced fibroblasts. J Immunol. 2001. 166:4507–4515.

28. Berry MA, Hargadon B, Shelley M, Parker D, Shaw DE, Green RH, Bradding P, Brightling CE, Wardlaw AJ, Pavord ID. Evidence of a role of tumor necrosis factor alpha in refractory asthma. N Engl J Med. 2006. 354:697–708.

29. Acosta-Rodriguez EV, Rivino L, Geginat J, Jarrossay D, Gattorno M, Lanzavecchia A, Sallusto F, Napolitani G. Surface phenotype and antigenic specificity of human interleukin 17-producing T helper memory cells. Nat Immunol. 2007. 8:639–646.

30. LeibundGut-Landmann S, Gross O, Robinson MJ, Osorio F, Slack EC, Tsoni SV, Schweighoffer E, Tybulewicz V, Brown GD, Ruland J, Reise Sousa C. Syk- and CARD9-dependent coupling of innate immunity to the induction of T helper cells that produce interleukin 17. Nat Immunol. 2007. 8:630–638.