Skip to main content
SpringerLink
Log in

IL-17-Producing NKT Cells in Airway Inflammation

  • Chapter
  • First Online:
TH17 Cells in Health and Disease

Abstract

Allergic asthma, the most common form of asthma, is thought to be mediated by allergen-specific TH2 cells, orchestrating a complex allergic inflammatory cascade. However, asthma is heterogeneous, and several other distinct forms of asthma have been recognized, and are associated with additional cellular and molecular pathways involving innate immunity, neutrophils, airway epithelial cells, and subsets of natural killer T (NKT) cells. A role for NKT cells in asthma has been suggested by extensive studies in several different animal models of asthma. This indicates that distinct subsets of NKT cells, some producing IL-17 and others inducing alternatively activated alveolar macrophages, function in concert with TH2 cells or independently of adaptive immunity in causing asthma. These studies greatly expand our understanding the cellular and molecular mechanisms that drive the development of asthma.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Agea, E., A. Russano, O. Bistoni, R. Mannucci, I. Nicoletti, L. Corazzi, A. Postle, G. De Libero, S. Porcelli, and F. Spinozzi. 2005. Human CD1-restricted T cell recognition of lipids from pollens. J Exp Med 202:295–308.

    Article  PubMed  CAS  Google Scholar 

  • Akbari, O., R.H. DeKruyff, and D.T. Umetsu. 2001. Pulmonary dendritic cells secreting IL-10 mediate T cell tolerance induced by respiratory exposure to antigen. Nat Immunol. 2:725–731.

    Article  PubMed  CAS  Google Scholar 

  • Akbari, O., J.L. Faul, E.G. Hoyte, G.J. Berry, J. Wahlstrom, M. Kronenberg, R.H. DeKruyff, and D.T. Umetsu. 2006. CD4+ invariant T-cell-receptor+ natural killer T cells in bronchial asthma. N Engl J Med 354:1117–1129.

    Article  PubMed  CAS  Google Scholar 

  • Akbari, O., G.J. Freeman, E.H. Meyer, E.A. Greenfield, T.T. Chang, A.H. Sharpe, G. Berry, R.H. DeKruyff, and D.T. Umetsu. 2002. Antigen-specific regulatory T cells develop via the ICOS-ICOS-Ligand pathway and inhibit allergen-induced airway hyperreactivity. Nat Medicine8:1024–1032.

    Article  CAS  Google Scholar 

  • Akbari, O., P. Stock, E. Meyer, M. Kronenberg, S. Sidobre, T. Nakayama, M. Taniguchi, M.J. Grusby, R.H. DeKruyff, and D.T. Umetsu. 2003. Essential role of NKT cells producing IL-4 and IL-13 in the development of allergen-induced airway hyperreactivity. Nat Medicine 9:582–588.

    Article  CAS  Google Scholar 

  • Akdis, C.A., T. Blesken, M. Akdis, B. Wuthrich, and K. Blaser. 1998. Role of interleukin 10 in specific immunotherapy. J Clin Invest. 102:98–106.

    Article  PubMed  CAS  Google Scholar 

  • Akdis, M., J. Verhagen, A. Taylor, F. Karamloo, C. Karagiannidis, R. Crameri, S. Thunberg, G. Deniz, R. Valenta, H. Fiebig, C. Kegel, R. Disch, C.B. Schmidt-Weber, K. Blaser, and C.A. Akdis. 2004. Immune responses in healthy and allergic individuals are characterized by a fine balance between allergen-specific T regulatory 1 and T helper 2 cells. J Exp Med199:1567–1575.

    Article  PubMed  CAS  Google Scholar 

  • Angkasekwinai, P., H. Park, Y.H. Wang, S.H. Chang, D.B. Corry, Y.J. Liu, Z. Zhu, and C. Dong. 2007. Interleukin 25 promotes the initiation of proallergic type 2 responses. J Exp Med204:1509–1517.

    Article  PubMed  CAS  Google Scholar 

  • Aris, R.M., D. Christian, P.Q. Hearne, K. Kerr, W.E. Finkbeiner, and J.R. Balmes. 1993. Ozone-induced airway inflammation in human subjects as determined by airway lavage and biopsy. Am Rev Respir Dis 148:1363–1372.

    Article  PubMed  CAS  Google Scholar 

  • Baekkevold, E.S., M. Roussigne, T. Yamanaka, F.E. Johansen, F.L. Jahnsen, F. Amalric, P. Brandtzaeg, M. Erard, G. Haraldsen, and J.P. Girard. 2003. Molecular characterization of NF-HEV, a nuclear factor preferentially expressed in human high endothelial venules. Am J Pathol 163:69–79.

    Article  PubMed  CAS  Google Scholar 

  • Ballantyne, S.J., J.L. Barlow, H.E. Jolin, P. Nath, A.S. Williams, K.F. Chung, G. Sturton, S.H. Wong, and A.N. McKenzie. 2007. Blocking IL-25 prevents airway hyperresponsiveness in allergic asthma. J Allergy Clin Immunol 120:1324–1331.

    Article  PubMed  CAS  Google Scholar 

  • Barrat, F.J., D.J. Cua, A. Boonstra, D.F. Richards, C. Crain, H.F. Savelkoul, R. de Waal-Malefyt, R.L. Coffman, C.M. Hawrylowicz, and A. O’Garra. 2002. In vitro generation of interleukin 10-producing regulatory CD4(+) T cells is induced by immunosuppressive drugs and inhibited by T helper type 1 (Th1)- and Th2-inducing cytokines. J Exp Med 195:603–616.

    Article  PubMed  CAS  Google Scholar 

  • Bendelac, A., P.B. Savage, and L. Teyton. 2007. The biology of NKT cells. Annu Rev Immunol25:297–336.

    Article  PubMed  CAS  Google Scholar 

  • Bourgeois, E., L.P. Van, M. Samson, S. Diem, A. Barra, S. Roga, J.M. Gombert, E. Schneider, M. Dy, P. Gourdy, J.P. Girard, and A. Herbelin. 2009. The pro-Th2 cytokine IL-33 directly interacts with invariant NKT and NK cells to induce IFN-gamma production. Eur J Immunol39:1046–1055.

    Article  PubMed  CAS  Google Scholar 

  • Bratke, K., P. Julius, and J.C. Virchow. 2007. Invariant natural killer T cells in obstructive pulmonary diseases. N Engl J Med 357:194; author reply 194–195.

    Google Scholar 

  • Braun-Fahrlander, C., J. Riedler, U. Herz, W. Eder, M. Waser, L. Grize, S. Maisch, D. Carr, F. Gerlach, A. Bufe, R. Lauener, R. Schierl, H. Renz, D. Nowak, and E. von Mutius. 2002. Environmental exposure to endotoxin and its relation to asthma in school-age children. N Engl J Med 347:869–877.

    Article  PubMed  Google Scholar 

  • Bullens, D.M., E. Truyen, L. Coteur, E. Dilissen, P.W. Hellings, L.J. Dupont, and J.L. Ceuppens. 2006. IL-17 mRNA in sputum of asthmatic patients: linking T cell driven inflammation and granulocytic influx? Respir Res 7:135.

    Article  PubMed  Google Scholar 

  • Busse, W.W., and R.F. Lemanske, Jr. 2001. Asthma. N Engl J Med 344:350–362.

    Article  PubMed  CAS  Google Scholar 

  • Chanez, P., S.E. Wenzel, G.P. Anderson, J.M. Anto, E.H. Bel, L.P. Boulet, C.E. Brightling, W.W. Busse, M. Castro, B. Dahlen, S.E. Dahlen, L.M. Fabbri, S.T. Holgate, M. Humbert, M. Gaga, G.F. Joos, B. Levy, K.F. Rabe, P.J. Sterk, S.J. Wilson, and I. Vachier. 2007. Severe asthma in adults: what are the important questions? J Allergy Clin Immunol 119:1337–1348.

    Article  PubMed  Google Scholar 

  • Cho, S.H., L.A. Stanciu, S.T. Holgate, and S.L. Johnston. 2005. Increased interleukin-4, interleukin-5, and interferon-gamma in airway CD4+ and CD8+ T cells in atopic asthma. Am J Respir Crit Care Med 171:224–230.

    Article  PubMed  Google Scholar 

  • Conrad, M.L., R. Ferstl, R. Teich, S. Brand, N. Blumer, A.O. Yildirim, C.C. Patrascan, A. Hanuszkiewicz, S. Akira, H. Wagner, O. Holst, E. von Mutius, P.I. Pfefferle, C.J. Kirschning, H. Garn, and H. Renz. 2009. Maternal TLR signaling is required for prenatal asthma protection by the nonpathogenic microbe Acinetobacter lwoffii F78. J Exp Med 206:2869–2877.

    Article  PubMed  CAS  Google Scholar 

  • Coquet, J.M., S. Chakravarti, K. Kyparissoudis, F.W. McNab, L.A. Pitt, B.S. McKenzie, S.P. Berzins, M.J. Smyth, and D.I. Godfrey. 2008. Diverse cytokine production by NKT cell subsets and identification of an IL-17-producing CD4-NK1.1- NKT cell population. Proc Natl Acad Sci USA 105:11287–11292.

    Article  PubMed  CAS  Google Scholar 

  • Das, J., P. Eynott, R. Jupp, A. Bothwell, L. Van Kaer, Y. Shi, and G. Das. 2006. Natural killer T cells and CD8+ T cells are dispensable for T cell-dependent allergic airway inflammation. Nat Med 12:1345–1346; author reply 1347.

    Google Scholar 

  • Fallon, P.G., S.J. Ballantyne, N.E. Mangan, J.L. Barlow, A. Dasvarma, D.R. Hewett, A. McIlgorm, H.E. Jolin, and A.N. McKenzie. 2006. Identification of an interleukin (IL)-25-dependent cell population that provides IL-4, IL-5, and IL-13 at the onset of helminth expulsion. J Exp Med203:1105–1116.

    Article  PubMed  CAS  Google Scholar 

  • Fort, M.M., J. Cheung, D. Yen, J. Li, S.M. Zurawski, S. Lo, S. Menon, T. Clifford, B. Hunte, R. Lesley, T. Muchamuel, S.D. Hurst, G. Zurawski, M.W. Leach, D.M. Gorman, and D.M. Rennick. 2001. IL-25 induces IL-4, IL-5, and IL-13 and Th2-associated pathologies in vivo. Immunity 15:985–995.

    Article  PubMed  CAS  Google Scholar 

  • Gavett, S.H., X. Chen, F. Finkelman, and M. Wills-Karp. 1994. Depletion of murine CD4+ T lymphocytes prevents antigen-induced airway hyperreactivity and pulmonary eosinophilia. Am J Respir Cell Mol Biol 10:587–593.

    PubMed  CAS  Google Scholar 

  • Gent, J.F., E.W. Triche, T.R. Holford, K. Belanger, M.B. Bracken, W.S. Beckett, and B.P. Leaderer. 2003. Association of low-level ozone and fine particles with respiratory symptoms in children with asthma. JAMA 290:1859–1867.

    Article  PubMed  CAS  Google Scholar 

  • Gern, J.E., and W.W. Busse. 2000. The role of viral infections in the natural history of asthma. J Allergy Clin Immunol 106:201–212.

    Article  PubMed  CAS  Google Scholar 

  • Goto, M., M. Murakawa, K. Kadoshima-Yamaoka, Y. Tanaka, K. Nagahira, Y. Fukuda, and T. Nishimura. 2009. Murine NKT cells produce Th17 cytokine interleukin-22. Cell Immunol 254:81–84.

    Article  PubMed  CAS  Google Scholar 

  • Green, R.H., C.E. Brightling, G. Woltmann, D. Parker, A.J. Wardlaw, and I.D. Pavord. 2002. Analysis of induced sputum in adults with asthma: identification of subgroup with isolated sputum neutrophilia and poor response to inhaled corticosteroids. Thorax 57:875–879.

    Article  PubMed  CAS  Google Scholar 

  • Haldar, P., and I.D. Pavord. 2007. Noneosinophilic asthma: a distinct clinical and pathologic phenotype. The Journal of allergy and clinical immunology 119:1043–1052; quiz 1053–1044.

    Google Scholar 

  • Hamelin, M.E., G.A. Prince, A.M. Gomez, R. Kinkead, and G. Boivin. 2006. Human metapneumovirus infection induces long-term pulmonary inflammation associated with airway obstruction and hyperresponsiveness in mice. J Infect Dis 193:1634–1642.

    Article  PubMed  Google Scholar 

  • Hammad, H., M. Chieppa, F. Perros, M.A. Willart, R.N. Germain, and B.N. Lambrecht. 2009. House dust mite allergen induces asthma via Toll-like receptor 4 triggering of airway structural cells. Nat Med 15:410–416.

    Article  PubMed  CAS  Google Scholar 

  • Hansen, G., G. Berry, R.H. DeKruyff, and D.T. Umetsu. 1999. Allergen-specific Th1 cells fail to counterbalance Th2 cell-induced airway hyperreactivity but cause severe airway inflammation. J Clin Invest 103:175–183.

    Article  PubMed  CAS  Google Scholar 

  • Hansen, G., J.J. McIntire, V.P. Yeung, G. Berry, G.J. Thorbecke, L. Chen, R.H. DeKruyff, and D.T. Umetsu. 2000. CD4+ Th Cells Engineered To Produce Latent TGF-b1 Reverse Allergen-Induced Airway Hyperreactivity and Inflammation. J Clin Invest 11:89–96.

    Google Scholar 

  • Kay, A.B. 1989. Inflammatory cells in bronchial asthma. J Asthma 26:335–344.

    Article  PubMed  CAS  Google Scholar 

  • Kim, E.Y., J.T. Battaile, A.C. Patel, Y. You, E. Agapov, M.H. Grayson, L.A. Benoit, D.E. Byers, Y. Alevy, J. Tucker, S. Swanson, R. Tidwell, J.W. Tyner, J.D. Morton, M. Castro, D. Polineni, G.A. Patterson, R.A. Schwendener, J.D. Allard, G. Peltz, and M.J. Holtzman. 2008. Persistent activation of an innate immune response translates respiratory viral infection into chronic lung disease. Nat Med 14:633–640.

    Article  PubMed  CAS  Google Scholar 

  • Kim, S., S. Lalani, V.V. Parekh, T.L. Vincent, L. Wu, and L. Van Kaer. 2008. Impact of bacteria on the phenotype, functions, and therapeutic activities of invariant NKT cells in mice. J Clin Invest 118:2301–2315.

    PubMed  CAS  Google Scholar 

  • Kinjo, Y., E. Tupin, D. Wu, M. Fujio, R. Garcia-Navarro, M.R. Benhnia, D.M. Zajonc, G. Ben-Menachem, G.D. Ainge, G.F. Painter, A. Khurana, K. Hoebe, S.M. Behar, B. Beutler, I.A. Wilson, M. Tsuji, T.J. Sellati, C.H. Wong, and M. Kronenberg. 2006. Natural killer T cells recognize diacylglycerol antigens from pathogenic bacteria. Nat Immunol 7:978–986.

    Article  PubMed  CAS  Google Scholar 

  • Kondo, Y., T. Yoshimoto, K. Yasuda, S. Futatsugi-Yumikura, M. Morimoto, N. Hayashi, T. Hoshino, J. Fujimoto, and K. Nakanishi. 2008. Administration of IL-33 induces airway hyperresponsiveness and goblet cell hyperplasia in the lungs in the absence of adaptive immune system. Int Immunol 20:791–800.

    Article  PubMed  CAS  Google Scholar 

  • Kreslavsky, T., A.K. Savage, R. Hobbs, F. Gounari, R. Bronson, P. Pereira, P.P. Pandolfi, A. Bendelac, and H. von Boehmer. 2009. TCR-inducible PLZF transcription factor required for innate phenotype of a subset of gammadelta T cells with restricted TCR diversity. Proc Natl Acad Sci USA 106:12453–12458.

    Article  PubMed  CAS  Google Scholar 

  • Kronenberg, M. 2005. Toward an understanding of NKT cell biology: progress and paradoxes. Annu Rev Immunol 23:877–900.

    Article  PubMed  CAS  Google Scholar 

  • Lambrecht, B.N., and H. Hammad. 2009. Biology of lung dendritic cells at the origin of asthma. Immunity 31:412–424.

    Article  PubMed  CAS  Google Scholar 

  • Leckie, M.J., A. ten Brinke, J. Khan, Z. Diamant, B.J. O’Connor, C.M. Walls, A.K. Mathur, H.C. Cowley, K.F. Chung, R. Djukanovic, T.T. Hansel, S.T. Holgate, P.J. Sterk, and P.J. Barnes. 2000. Effects of an interleukin-5 blocking monoclonal antibody on eosinophils, airway hyper-responsiveness, and the late asthmatic response. Lancet 356:2144–2148.

    Article  PubMed  CAS  Google Scholar 

  • Lee, K.A., M.H. Kang, Y.S. Lee, Y.J. Kim, D.H. Kim, H.J. Ko, and C.Y. Kang. 2008. A distinct subset of natural killer T cells produces IL-17, contributing to airway infiltration of neutrophils but not to airway hyperreactivity. Cell Immunol 251:50–55.

    Article  PubMed  CAS  Google Scholar 

  • Letuve, S., S. Lajoie-Kadoch, S. Audusseau, M.E. Rothenberg, P.O. Fiset, M.S. Ludwig, and Q. Hamid. 2006. IL-17E upregulates the expression of proinflammatory cytokines in lung fibroblasts. J Allergy Clin Immunol 117:590–596.

    Article  PubMed  CAS  Google Scholar 

  • Lewkowich, I.P., N.S. Herman, K.W. Schleifer, M.P. Dance, B.L. Chen, K.M. Dienger, A.A. Sproles, J.S. Shah, J. Kohl, Y. Belkaid, and M. Wills-Karp. 2005. CD4+CD25+ T cells protect against experimentally induced asthma and alter pulmonary dendritic cell phenotype and function. J Exp Med 202:1549–1561.

    Article  PubMed  CAS  Google Scholar 

  • Liu, Y.J. 2009. TSLP in epithelial cell and dendritic cell cross talk. Adv Immunol 101:1–25.

    Article  PubMed  CAS  Google Scholar 

  • Liu, Y.J., V. Soumelis, N. Watanabe, T. Ito, Y.H. Wang, W. Malefyt Rde, M. Omori, B. Zhou, and S.F. Ziegler. 2007. TSLP: an epithelial cell cytokine that regulates T cell differentiation by conditioning dendritic cell maturation. Annu Rev Immunol 25:193–219.

    Article  PubMed  CAS  Google Scholar 

  • Martinez, F.D., A.L. Wright, L.M. Taussig, C.J. Holberg, M. Halonen, W.J. Morgan, and G.H. Associates. 1995. Asthma and wheezing in the first six years of life. New Engl J Med 332:133–138.

    Article  Google Scholar 

  • Matangkasombut, P., G. Marigowda, A. Irvine, I. Idris, M. Pichavant, H. Kim, Y. Yasumi, S. Wilson, R. DeKruyff, J.L. Faul, E. Israel, O. Akbari, and D.T. Umetsu. 2009. Natural Killer T Cells in the Lungs of Patients with Asthma. J Allergy Clin Immunol 123:1181–1185.

    Article  PubMed  CAS  Google Scholar 

  • Matangkasombut, P., M. Pichavant, R.H. Dekruyff, and D.T. Umetsu. 2009. Natural killer T cells and the regulation of asthma. Mucosal Immunol 2:383–392.

    Article  PubMed  CAS  Google Scholar 

  • Matangkasombut, P., M. Pichavant, T. Yasumi, C. Hendricks, P.B. Savage, R.H. Dekruyff, and D.T. Umetsu. 2008. Direct activation of natural killer T cells induces airway hyperreactivity in nonhuman primates. J Allergy Clin Immunol 121:1287–1289.

    Article  PubMed  CAS  Google Scholar 

  • Matricardi, P., F. Rosmini, S. Riondino, M. Fortini, L. Ferrigno, M. Rapicetta, and S. Bonini. 2000. Exposure to foodborne and orofecal microbes versus airborne viruses in relation to atopy and allergic asthma: epidemiological study. BMJ 320:412–417.

    Article  PubMed  CAS  Google Scholar 

  • Matricardi, P.M., F. Rosmini, V. Panetta, L. Ferrigno, and S. Bonini. 2002. Hay fever and asthma in relation to markers of infection in the United States. J Allergy Clin Immunol 110:381–387.

    Article  PubMed  Google Scholar 

  • McMenamin, C., and P.G. Holt. 1993. The natural immune response to inhaled soluble protein antigens involves major histocompatibility complex (MHC) class I-restricted CD8+ T cell-mediated but MHC class II-restricted CD4+ T cell-dependent immune deviation resulting in selective suppression of immunoglobulin E production. J Exp Med 178:889–899.

    Article  PubMed  CAS  Google Scholar 

  • Meyer, E.H., S. Goya, O. Akbari, G.J. Berry, P.B. Savage, M. Kronenberg, T. Nakayama, R.H. DeKruyff, and D.T. Umetsu. 2006. Glycolipid activation of invariant T cell receptor+ NK T cells is sufficient to induce airway hyperreactivity independent of conventional CD4+ T cells. Proc Natl Acad Sci USA 103:2782–2787.

    Article  PubMed  CAS  Google Scholar 

  • Meyer, E.H., M.A. Wurbel, T.L. Staton, M. Pichavant, M.J. Kan, P.B. Savage, R.H. DeKruyff, E.C. Butcher, J.J. Campbell, and D.T. Umetsu. 2007. iNKT cells require CCR4 to localize to the airways and to induce airway hyperreactivity. J Immunol 179:4661–4671.

    PubMed  CAS  Google Scholar 

  • Michel, M.L., A.C. Keller, C. Paget, M. Fujio, F. Trottein, P.B. Savage, C.H. Wong, E. Schneider, M. Dy, and M.C. Leite-de-Moraes. 2007. Identification of an IL-17-producing NK1.1(neg) iNKT cell population involved in airway neutrophilia. J Exp Med 204:995–1001.

    Article  PubMed  CAS  Google Scholar 

  • Moro, K., T. Yamada, M. Tanabe, T. Takeuchi, T. Ikawa, H. Kawamoto, J. Furusawa, M. Ohtani, H. Fujii, and S. Koyasu. 2010. Innate production of T(H)2 cytokines by adipose tissue-associated c-Kit(+)Sca-1(+) lymphoid cells. Nature 463:540–544.

    Article  PubMed  CAS  Google Scholar 

  • Mutalithas, K., J. Croudace, C. Guillen, S. Siddiqui, D. Thickett, and A. Wardlaw. 2007. Bronchoalveolar lavage invariant natural killer T cells are not increased in asthma. J Allergy Clin Immunol 119:1274–1276.

    Article  PubMed  CAS  Google Scholar 

  • Nagata, Y., H. Kamijuku, M. Taniguchi, S. Ziegler, and K. Seino. 2007. Differential role of thymic stromal lymphopoietin in the induction of airway hyperreactivity and Th2 immune response in antigen-induced asthma with respect to natural killer T cell function. Int Arch Allergy Immunol144:305–314.

    Article  PubMed  CAS  Google Scholar 

  • Nakao, F., K. Ihara, K. Kusuhara, Y. Sasaki, N. Kinukawa, A. Takabayashi, S. Nishima, and T. Hara. 2001. Association of IFN-gamma and IFN regulatory factor 1 polymorphisms with childhood atopic asthma. J Allergy Clin immunol 107:499–504.

    Article  PubMed  CAS  Google Scholar 

  • Oboki, K., T. Ohno, H. Saito, and S. Nakae. 2008. Th17 and allergy. Allergol Int 57:121–134.

    Article  PubMed  CAS  Google Scholar 

  • Oh, J.W., C.M. Seroogy, E.H. Meyer, O. Akbari, G. Berry, C.G. Fathman, R.H. DeKruyff, and D.T. Umetsu. 2002. CD4 T helper cells engineered to produce IL-10 reverse allergen-induced airway hyperreactivity and inflammation. J Allergy Clin Immunol 110:460–468.

    Article  PubMed  CAS  Google Scholar 

  • Ostroukhova, M., C. Seguin-Devaux, T.B. Oriss, B. Dixon-McCarthy, L. Yang, B.T. Ameredes, T.E. Corcoran, and A. Ray. 2004. Tolerance induced by inhaled antigen involves CD4(+) T cells expressing membrane-bound TGF-beta and FOXP3. J Clin Invest114:28–38.

    PubMed  CAS  Google Scholar 

  • Ownby, D., C. Johnson, and E. Peterson. 2002. Exposure to dogs and cats in the first year of life and risk of allergic sensitization at 6 to 7 years of age. JAMA 288:963–972.

    Article  PubMed  Google Scholar 

  • Owyang, A.M., C. Zaph, E.H. Wilson, K.J. Guild, T. McClanahan, H.R. Miller, D.J. Cua, M. Goldschmidt, C.A. Hunter, R.A. Kastelein, and D. Artis. 2006. Interleukin 25 regulates type 2 cytokine-dependent immunity and limits chronic inflammation in the gastrointestinal tract. J Exp Med 203:843–849.

    Article  PubMed  Google Scholar 

  • Perrigoue, J.G., S.A. Saenz, M.C. Siracusa, E.J. Allenspach, B.C. Taylor, P.R. Giacomin, M.G. Nair, Y. Du, C. Zaph, N. van Rooijen, M.R. Comeau, E.J. Pearce, T.M. Laufer, and D. Artis. 2009. MHC class II-dependent basophil-CD4+ T cell interactions promote T(H)2 cytokine-dependent immunity. Nat Immunol 10:697–705.

    Article  PubMed  CAS  Google Scholar 

  • Pesce, J., M. Kaviratne, T.R. Ramalingam, R.W. Thompson, J.F. Urban, Jr., A.W. Cheever, D.A. Young, M. Collins, M.J. Grusby, and T.A. Wynn. 2006. The IL-21 receptor augments Th2 effector function and alternative macrophage activation. J Clin Invest116:2044–2055.

    Article  PubMed  CAS  Google Scholar 

  • Pichavant, M., S. Goya, E.H. Meyer, R.A. Johnston, H.Y. Kim, P. Matangkasombut, M. Zhu, Y. Iwakura, P.B. Savage, R.H. DeKruyff, S.A. Shore, and D.T. Umetsu. 2008. Ozone exposure in a mouse model induces airway hyperreactivity that requires the presence of natural killer T cells and IL-17. J Exp Med 205:385–393.

    Article  PubMed  CAS  Google Scholar 

  • Rachitskaya, A.V., A.M. Hansen, R. Horai, Z. Li, R. Villasmil, D. Luger, R.B. Nussenblatt, and R.R. Caspi. 2008. Cutting edge: NKT cells constitutively express IL-23 receptor and RORgammat and rapidly produce IL-17 upon receptor ligation in an IL-6-independent fashion.J Immunol180:5167–5171.

    PubMed  CAS  Google Scholar 

  • Reynolds, C., J. Barkans, P. Clark, H. Kariyawasam, D. Altmann, B. Kay, and R. Boyton. 2009. Natural killer T cells in bronchial biopsies from human allergen challenge model of allergic asthma. J Allergy Clin Immunol 124:860-862; author reply 862.

    Google Scholar 

  • Riedler, J., C. Braun-Fahrlander, W. Eder, M. Schreuer, M. Waser, S. Maisch, D. Carr, R. Schierl, D. Nowak, and E. von Mutius. 2001. Exposure to farming in early life and development of asthma and allergy: a cross-sectional survey. Lancet 358:1129–1133.

    Article  PubMed  CAS  Google Scholar 

  • Robinson, D.S., Q. Hamid, S. Ying, A. Tsicopoulos, J. Barkans, A.M. Bentley, C. Corrigan, S.R. Durham, and A.B. Kay. 1992. Predominant TH2-like bronchoalveolar T-lymphocyte population in atopic asthma. N Engl J Med 326:298–304.

    Article  PubMed  CAS  Google Scholar 

  • Savage, A.K., M.G. Constantinides, J. Han, D. Picard, E. Martin, B. Li, O. Lantz, and A. Bendelac. 2008. The transcription factor PLZF directs the effector program of the NKT cell lineage. Immunity 29:391–403.

    Article  PubMed  CAS  Google Scholar 

  • Schmitz, J., A. Owyang, E. Oldham, Y. Song, E. Murphy, T.K. McClanahan, G. Zurawski, M. Moshrefi, J. Qin, X. Li, D.M. Gorman, J.F. Bazan, and R.A. Kastelein. 2005. IL-33, an interleukin-1-like cytokine that signals via the IL-1 receptor-related protein ST2 and induces T helper type 2-associated cytokines. Immunity 23:479–490.

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Shi, H.Z., A. Humbles, C. Gerard, Z. Jin, and P.F. Weller. 2000. Lymph node trafficking and antigen presentation by endobronchial eosinophils. J Clin Invest 105:945–953.

    Article  PubMed  CAS  Google Scholar 

  • Sigurs, N., P.M. Gustafsson, R. Bjarnason, F. Lundberg, S. Schmidt, F. Sigurbergsson, and B. Kjellman. 2005. Severe respiratory syncytial virus bronchiolitis in infancy and asthma and allergy at age 13. Am J Respir Crit Care Med 171:137–141.

    Article  PubMed  Google Scholar 

  • Simpson, J.L., T.V. Grissell, J. Douwes, R.J. Scott, M.J. Boyle, and P.G. Gibson. 2007. Innate immune activation in neutrophilic asthma and bronchiectasis. Thorax 62:211–218.

    Article  PubMed  Google Scholar 

  • Smithgall, M.D., M.R. Comeau, B.R. Yoon, D. Kaufman, R. Armitage, and D.E. Smith. 2008. IL-33 amplifies both Th1- and Th2-type responses through its activity on human basophils, allergen-reactive Th2 cells, iNKT and NK cells. Int Immunol 20:1019–1030.

    Article  PubMed  CAS  Google Scholar 

  • Stock, P., O. Akbari, G. Berry, G. Freeman, R. DeKruyff, and D.T. Umetsu. 2004. Induction of TH1-like regulatory cells that express Foxp3 and protect against airway hyperreactivity. Nat Immunol. 5:1149–1156.

    Article  PubMed  CAS  Google Scholar 

  • Stock, P., V. Lombardi, V. Kohlrautz, and O. Akbari. 2009. Induction of airway hyperreactivity by IL-25 is dependent on a subset of invariant NKT cells expressing IL-17RB. J Immunol182:5116–5122.

    Article  PubMed  CAS  Google Scholar 

  • Subrata, L.S., J. Bizzintino, E. Mamessier, A. Bosco, K.L. McKenna, M.E. Wikstrom, J. Goldblatt, P.D. Sly, B.J. Hales, W.R. Thomas, I.A. Laing, P.N. LeSouef, and P.G. Holt. 2009. Interactions between innate antiviral and atopic immunoinflammatory pathways precipitate and sustain asthma exacerbations in children. J Immunol 183:2793–2800.

    Article  PubMed  CAS  Google Scholar 

  • Tamachi, T., Y. Maezawa, K. Ikeda, S. Kagami, M. Hatano, Y. Seto, A. Suto, K. Suzuki, N. Watanabe, Y. Saito, T. Tokuhisa, I. Iwamoto, and H. Nakajima. 2006. IL-25 enhances allergic airway inflammation by amplifying a TH2 cell-dependent pathway in mice. J Allergy Clin Immunol 118:606–614.

    Article  PubMed  CAS  Google Scholar 

  • Terashima, A., H. Watarai, S. Inoue, E. Sekine, R. Nakagawa, K. Hase, C. Iwamura, H. Nakajima, T. Nakayama, and M. Taniguchi. 2008. A novel subset of mouse NKT cells bearing the IL-17 receptor B responds to IL-25 and contributes to airway hyperreactivity. J Exp Med205:2727–2733.

    Article  PubMed  CAS  Google Scholar 

  • Thomas, S.Y., C.M. Lilly, and A.D. Luster. 2006. Invariant natural killer T cells in bronchial asthma (correspondence). N Engl J Med 354:2613–2616.

    Article  PubMed  CAS  Google Scholar 

  • Trompette, A., S. Divanovic, A. Visintin, C. Blanchard, R.S. Hegde, R. Madan, P.S. Thorne, M. Wills-Karp, T.L. Gioannini, J.P. Weiss, and C.L. Karp. 2009. Allergenicity resulting from functional mimicry of a Toll-like receptor complex protein. Nature 457:585–588.

    Article  PubMed  CAS  Google Scholar 

  • Verhasselt, V., V. Milcent, J. Cazareth, A. Kanda, S. Fleury, D. Dombrowicz, N. Glaichenhaus, and V. Julia. 2008. Breast milk-mediated transfer of an antigen induces tolerance and protection from allergic asthma. Nat Med 14:170–175.

    Article  PubMed  CAS  Google Scholar 

  • Vijayanand, P., G. Seumois, C. Pickard, R.M. Powell, G. Angco, D. Sammut, S.D. Gadola, P.S. Friedmann, and R. Djukanovic. 2007. Invariant natural killer T cells in asthma and chronic obstructive pulmonary disease. N Engl J Med356:1410–1422.

    Article  PubMed  CAS  Google Scholar 

  • Watanabe, N., S. Hanabuchi, M.A. Marloie-Provost, S. Antonenko, Y.J. Liu, and V. Soumelis. 2005. Human TSLP promotes CD40 ligand-induced IL-12 production by myeloid dendritic cells but maintains their Th2 priming potential. Blood 105:4749–4751.

    Article  PubMed  CAS  Google Scholar 

  • Wenzel, S., D. Wilbraham, R. Fuller, E.B. Getz, and M. Longphre. 2007. Effect of an interleukin-4 variant on late phase asthmatic response to allergen challenge in asthmatic patients: results of two phase 2a studies. Lancet 370:1422–1431.

    Article  PubMed  CAS  Google Scholar 

  • Wills-Karp, M. 1999. Immunologic basis of antigen-induced airway hyperresponsiveness. Annu Rev Immunol 17:255–281.

    Article  PubMed  CAS  Google Scholar 

  • Wills-Karp, M., and S.L. Ewart. 1997. The genetics of allergen-induced airway hyperresponsiveness in mice. Am J Respir Crit Care Med 156:S89–96.

    PubMed  CAS  Google Scholar 

  • Wills-Karp, M., J. Luyimbazi, X. Xu, B. Schofield, T.Y. Neben, C.L. Karp, and D.D. Donaldson. 1998. Interleukin-13: central mediator of allergic asthma. Science 282:2258–2261.

    Article  PubMed  CAS  Google Scholar 

  • Wilson, R.H., G.S. Whitehead, H. Nakano, M.E. Free, J.K. Kolls, and D.N. Cook. 2009. Allergic sensitization through the airway primes Th17-dependent neutrophilia and airway hyperresponsiveness. Am J Respir Crit Care Med 180:720–730.

    Article  PubMed  CAS  Google Scholar 

  • Xystrakis, E., S. Kusumakar, S. Boswell, E. Peek, Z. Urry, D.F. Richards, T. Adikibi, C. Pridgeon, M. Dallman, T.K. Loke, D.S. Robinson, F.J. Barrat, A. O’Garra, P. Lavender, T.H. Lee, C. Corrigan, and C.M. Hawrylowicz. 2006. Reversing the defective induction of IL-10-secreting regulatory T cells in glucocorticoid-resistant asthma patients. J Clin Invest116:146–155.

    Article  PubMed  CAS  Google Scholar 

  • Zuany-Amorim C, Sawicka E, Manlius C, Le Moine A, Brunet LR, Kemeny DM, Bowen G, Rook G, and Walker C. 2002. Suppression of airway eosinophilia by killed Mycobacterium vaccae-induced allergen-specific regulatory T-cells. Nat Med 8:8625–8629.

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Immunology and Allergy, Children’s Hospital, Harvard Medical School, Boston, MA, 02115, USA

    Dale T. Umetsu

Authors
  1. Dale T. Umetsu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Rosemarie H. DeKruyff
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Dale T. Umetsu .

Editor information

Editors and Affiliations

  1. King's College London, Department of Nephrology and Transplanta, Guy's Hospital, London, WC2R 2LS, United Kingdom

    Shuiping Jiang

Rights and permissions

Reprints and permissions

Copyright information

© 2011 Springer Science+Business Media, LLC

About this chapter

Cite this chapter

Umetsu, D.T., DeKruyff, R.H. (2011). IL-17-Producing NKT Cells in Airway Inflammation. In: Jiang, S. (eds) TH17 Cells in Health and Disease. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-9371-7_27

Download citation

Publish with us

Policies and ethics

Search

Navigation