About this Journal Submit a Manuscript Table of Contents
Journal of Allergy
Volume 2010 (2010), Article ID 519298, 14 pages
http://dx.doi.org/10.1155/2010/519298
Review Article

The Other T Helper Cells in Asthma Pathogenesis

1Department of Experimental Pneumology, Research Center Borstel, 23845 Borstel, Germany
2Medical Clinic, Research Center Borstel, 23845 Borstel, Germany

Received 10 March 2010; Accepted 18 June 2010

Academic Editor: Kurt Blaser

Copyright © 2010 Christina Vock et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. J. Bousquet, P. K. Jeffery, W. W. Busse, M. Johnson, and A. M. Vignola, “Asthma. From bronchoconstriction to airways inflammation and remodeling,” American Journal of Respiratory and Critical Care Medicine, vol. 161, no. 5, pp. 1720–1745, 2000. View at Scopus
  2. M. Wegmann, “Th2 cells as targets for therapeutic intervention in allergic bronchial asthma,” Expert Review of Molecular Diagnostics, vol. 9, no. 1, pp. 85–100, 2009. View at Publisher · View at Google Scholar · View at Scopus
  3. M. Messi, I. Giacchetto, K. Nagata, A. Lanzavecchia, G. Natoli, and F. Sallusto, “Memory and flexibility of cytokine gene expression as separable properties of human TH1 and TH2 lymphocytes,” Nature Immunology, vol. 4, no. 1, pp. 78–86, 2003. View at Publisher · View at Google Scholar · View at Scopus
  4. M. Wills-Karp, J. Luyimbazi, X. Xu et al., “Interleukin-13: central mediator of allergic asthma,” Science, vol. 282, no. 5397, pp. 2258–2261, 1998. View at Publisher · View at Google Scholar · View at Scopus
  5. L. B. Bacharier and R. S. Geha, “Molecular mechanisms of IgE regulation,” Journal of Allergy and Clinical Immunology, vol. 105, no. 2, pp. S547–S558, 2000. View at Scopus
  6. J.-C. Renauld, “New insights into the role of cytokines in asthma,” Journal of Clinical Pathology, vol. 54, no. 8, pp. 577–589, 2001. View at Publisher · View at Google Scholar · View at Scopus
  7. H. F. Rosenberg, S. Phipps, and P. S. Foster, “Eosinophil trafficking in allergy and asthma,” Journal of Allergy and Clinical Immunology, vol. 119, no. 6, pp. 1303–1310, 2007. View at Publisher · View at Google Scholar · View at Scopus
  8. M. Wills-Karp, “Interleukin-13 in asthma pathogenesis,” Immunological Reviews, vol. 202, pp. 175–190, 2004. View at Publisher · View at Google Scholar · View at Scopus
  9. G. G. Brusselle, J. C. Kips, J. H. Tavernier et al., “Attenuation of allergic airway inflammation in IL-4 deficient mice,” Clinical and Experimental Allergy, vol. 24, no. 1, pp. 73–80, 1994. View at Publisher · View at Google Scholar · View at Scopus
  10. D. M. Walter, J. J. McIntire, G. Berry et al., “Critical role for IL-13 in the development of allergen-induced airway hyperreactivity,” Journal of Immunology, vol. 167, no. 8, pp. 4668–4675, 2001. View at Scopus
  11. P. S. Foster, S. P. Hogan, A. J. Ramsay, K. I. Matthaei, and I. G. Young, “Interleukin 5 deficiency abolishes eosinophilia, airways hyperreactivity, and lung damage in a mouse asthma model,” Journal of Experimental Medicine, vol. 183, no. 1, pp. 195–201, 1996. View at Publisher · View at Google Scholar · View at Scopus
  12. M. Wegmann and H. P. Hauber, “Experimental approaches towards allergic asthma therapy-murine asthma models,” Recent Patents on Inflammation and Allergy Drug Discovery, vol. 4, no. 1, pp. 37–53, 2010. View at Publisher · View at Google Scholar · View at Scopus
  13. L. C. Borish, H. S. Nelson, M. J. Lanz et al., “Interleukin-4 receptor in moderate atopic asthma. A phase I/II randomized, placebo-controlled trial,” American Journal of Respiratory and Critical Care Medicine, vol. 160, no. 6, pp. 1816–1823, 1999. View at Scopus
  14. M. J. Leckie, A. Ten Brinke, J. Khan et al., “Effects of an interleukin-5 blocking monoclonal antibody on eosinophils, airway hyper-responsiveness, and the late asthmatic response,” Lancet, vol. 356, pp. 2144–2148, 2000. View at Publisher · View at Google Scholar · View at Scopus
  15. S. Wenzel, D. Wilbraham, R. Fuller, E. B. Getz, and M. Longphre, “Effect of an interleukin-4 variant on late phase asthmatic response to allergen challenge in asthmatic patients: results of two phase 2a studies,” Lancet, vol. 370, no. 9596, pp. 1422–1431, 2007. View at Publisher · View at Google Scholar · View at Scopus
  16. S. Sel, M. Wegmann, S. Sel et al., “Immunomodulatory effects of viral TLR ligands on experimental asthma depend on the additive effects of IL-12 and IL-10,” Journal of Immunology, vol. 178, no. 12, pp. 7805–7813, 2007. View at Scopus
  17. P. Monteyne, J.-C. Renauld, J. Van Broeck, D. W. Dunne, F. Brombacher, and J.-P. Coutelier, “IL-4-independent regulation of in vivo IL-9 expression,” Journal of Immunology, vol. 159, no. 6, pp. 2616–2623, 1997. View at Scopus
  18. A. Shimbara, P. Christodoulopoulos, A. Soussi-Gounni et al., “IL-9 and its receptor in allergic and nonallergic lung disease: increased expression in asthma,” Journal of Allergy and Clinical Immunology, vol. 105, no. 1 I, pp. 108–115, 2000. View at Scopus
  19. V. J. Erpenbeck, J. M. Hohlfeld, B. Volkmann et al., “Segmental allergen challenge in patients with atopic asthma leads to increased IL-9 expression in bronchoalveolar lavage fluid lymphocytes,” Journal of Allergy and Clinical Immunology, vol. 111, no. 6, pp. 1319–1327, 2003. View at Publisher · View at Google Scholar · View at Scopus
  20. M. Veldhoen, C. Uyttenhove, J. van Snick et al., “Transforming growth factor-β 'reprograms' the differentiation of T helper 2 cells and promotes an interleukin 9-producing subset,” Nature Immunology, vol. 9, no. 12, pp. 1341–1346, 2008. View at Publisher · View at Google Scholar · View at Scopus
  21. V. Dardalhon, A. Awasthi, H. Kwon et al., “IL-4 inhibits TGF-β-induced Foxp3+ T cells and, together with TGF-β, generates IL-9+ IL-10+ Foxp3- effector T cells,” Nature Immunology, vol. 9, no. 12, pp. 1347–1355, 2008. View at Publisher · View at Google Scholar · View at Scopus
  22. J. Zhu, B. Min, J. Hu-Li et al., “Conditional deletion of Gata3 shows its essential function in TH1-TH2 responses,” Nature Immunology, vol. 5, no. 11, pp. 1157–1165, 2004. View at Publisher · View at Google Scholar · View at Scopus
  23. F. A. Houssiau, L. Schandene, M. Stevens et al., “A cascade of cytokines is responsible for IL-9 expression in human T cells: involvement of IL-2, IL-4, and IL-10,” Journal of Immunology, vol. 154, no. 6, pp. 2624–2630, 1995. View at Scopus
  24. A. Jäger, V. Dardalhon, R. A. Sobel, E. Bettelli, and V. K. Kuchroo, “Th1, Th17, and Th9 effector cells induce experimental autoimmune encephalomyelitis with different pathological phenotypes,” Journal of Immunology, vol. 183, no. 11, pp. 7169–7177, 2009. View at Publisher · View at Google Scholar · View at Scopus
  25. K. F. Hoffmann, A. W. Cheever, and T. A. Wynn, “IL-10 and the dangers of immune polarization: excessive type 1 and type 2 cytokine responses induce distinct forms of lethal immunopathology in murine schistosomiasis,” Journal of Immunology, vol. 164, no. 12, pp. 6406–6416, 2000. View at Scopus
  26. C. Li, I. Corraliza, and J. Langhorne, “A defect in interleukin-10 leads to enhanced malarial disease in Plasmodium chabaudi chabaudi infection in mice,” Infection and Immunity, vol. 67, no. 9, pp. 4435–4442, 1999. View at Scopus
  27. R. T. Gazzinelli, I. P. Oswald, S. L. James, and A. Sher, “IL-10 inhibits parasite killing and nitrogen oxide production by IFN-γ- activated macrophages,” Journal of Immunology, vol. 148, no. 6, pp. 1792–1796, 1992. View at Scopus
  28. B. H. Van Leeuwen, M. E. Martinson, G. C. Webb, and I. G. Young, “Molecular organization of the cytokine gene cluster, involving the human IL-3, IL-4, IL-5, and GM-CSF genes, on human chromosome 5,” Blood, vol. 73, no. 5, pp. 1142–1148, 1989. View at Scopus
  29. D. S. Postma, E. R. Bleecker, P. J. Amelung et al., “Genetic susceptibility to asthma—bronchial hyperresponsiveness coinherited with a major gene for atopy,” New England Journal of Medicine, vol. 333, no. 14, pp. 894–900, 1995. View at Publisher · View at Google Scholar · View at Scopus
  30. J.-C. Renaud, A. Kermouni, A. Vink, J. Louahed, and J. Van Snick, “Interleukin-9 and its receptor: involvement in mast cell differentiation and T cell oncogenesis,” Journal of Leukocyte Biology, vol. 57, no. 3, pp. 353–360, 1995. View at Scopus
  31. J. R. Gordon, P. R. Burd, and S. J. Galli, “Mast cells as a source of multifunctional cytokines,” Immunology Today, vol. 11, no. 12, pp. 458–464, 1990. View at Scopus
  32. P. Bradding, “Human mast cell cytokines,” Clinical and Experimental Allergy, vol. 26, no. 1, pp. 13–19, 1996. View at Publisher · View at Google Scholar · View at Scopus
  33. L. Hültner, S. Kölsch, M. Stassen et al., “In activated mast cells, IL-1 up-regulates the production of several Th2-related cytokines including IL-9,” Journal of Immunology, vol. 164, no. 11, pp. 5556–5563, 2000. View at Scopus
  34. A. S. Gounni, E. Nutku, L. Koussih et al., “IL-9 expression by human eosinophils: regulation by IL-1β and TNF-α,” Journal of Allergy and Clinical Immunology, vol. 106, no. 3, pp. 460–466, 2000. View at Publisher · View at Google Scholar · View at Scopus
  35. L. Hultner, C. Druez, J. Moeller et al., “Mast cell growth-enhancing activity (MEA) is structurally related and functionally identical to the novel mouse T cell growth factor P40/TCGFIII (interleukin 9),” European Journal of Immunology, vol. 20, no. 6, pp. 1413–1416, 1990. View at Publisher · View at Google Scholar · View at Scopus
  36. J. Louahed, A. Kermouni, J. Van Snick, and J.-C. Renauld, “IL-9 induces expression of granzymes and high-affinity IgE receptor in murine T helper clones,” Journal of Immunology, vol. 154, no. 10, pp. 5061–5070, 1995. View at Scopus
  37. J. Van Snick, A. Goethals, J.-C. Renauld et al., “Cloning and characterization of a cDNA for a new mouse T cell growth factor [P40],” Journal of Experimental Medicine, vol. 169, no. 1, pp. 363–368, 1989. View at Scopus
  38. A. Gessner, H. Blum, and M. Rollinghoff, “Differential regulation of IL-9-expression after infection with Leishmania major in susceptible and resistant mice,” Immunobiology, vol. 189, no. 5, pp. 419–435, 1993. View at Scopus
  39. U.-A. Temann, G. P. Geba, J. A. Rankin, and R. A. Flavell, “Expression of interleukin 9 in the lungs of transgenic mice causes airway inflammation, mast cell hyperplasia, and bronchial hyperresponsiveness,” Journal of Experimental Medicine, vol. 188, no. 7, pp. 1307–1320, 1998. View at Publisher · View at Google Scholar · View at Scopus
  40. M. P. McLane, A. Haczku, M. Van De Rijn et al., “Interleukin-9 promotes allergen-induced eosinophilic inflammation and airway hyperresponsiveness in transgenic mice,” American Journal of Respiratory Cell and Molecular Biology, vol. 19, no. 5, pp. 713–720, 1998. View at Scopus
  41. A. Vink, G. Warnier, F. Brombacher, and J.-C. Renauld, “Interleukin 9-induced in vivo expansion of the B-1 lymphocyte population,” Journal of Experimental Medicine, vol. 189, no. 9, pp. 1413–1423, 1999. View at Publisher · View at Google Scholar · View at Scopus
  42. J. Louahed, Y. Zhou, W. Lee Maloy et al., “Interleukin 9 promotes influx and local maturation of eosinophils,” Blood, vol. 97, no. 4, pp. 1035–1042, 2001. View at Publisher · View at Google Scholar · View at Scopus
  43. A. S. Gounni, B. Gregory, E. Nutku et al., “Interleukin-9 enhances interleukin-5 receptor expression, differentiation, and survival of human eosinophils,” Blood, vol. 96, no. 6, pp. 2163–2171, 2000. View at Scopus
  44. Q. Dong, J. Louahed, A. Vink et al., “IL-9 induces chemokine expression in lung epithelial cells and baseline airway eosinophilia in transgenic mice,” European Journal of Immunology, vol. 29, no. 7, pp. 2130–2139, 1999. View at Publisher · View at Google Scholar · View at Scopus
  45. F. F. Little, W. W. Cruikshank, and D. M. Center, “IL-9 stimulates release of chemotactic factors from human bronchial epithelial cells,” American Journal of Respiratory Cell and Molecular Biology, vol. 25, no. 3, pp. 347–352, 2001. View at Scopus
  46. J. Louahed, M. Toda, J. Jen et al., “Interleukin-9 upregulates mucus expression in the airways,” American Journal of Respiratory Cell and Molecular Biology, vol. 22, no. 6, pp. 649–656, 2000. View at Scopus
  47. M. Longphre, D. Li, M. Gallup et al., “Allergen-induced IL-9 directly stimulates mucin transcription in respiratory epithelial cells,” Journal of Clinical Investigation, vol. 104, no. 10, pp. 1375–1382, 1999. View at Scopus
  48. N. C. Nicolaides, K. J. Holroyd, S. L. Ewart et al., “Interleukin 9: a candidate gene for asthma,” Proceedings of the National Academy of Sciences of the United States of America, vol. 94, no. 24, pp. 13175–13180, 1997. View at Publisher · View at Google Scholar · View at Scopus
  49. S. G. Abdelilah, K. Latifa, N. Esra et al., “Functional expression of IL-9 receptor by human neutrophils from asthmatic donors: role in IL-8 release,” Journal of Immunology, vol. 166, no. 4, pp. 2768–2774, 2001. View at Scopus
  50. J. A. Rankin, D. E. Picarella, G. P. Geba et al., “Phenotypic and physiologic characterization of transgenic mice expressing interleukin 4 in the lung: lymphocytic and eosinophilic inflammation without airway hyperreactivity,” Proceedings of the National Academy of Sciences of the United States of America, vol. 93, no. 15, pp. 7821–7825, 1996. View at Publisher · View at Google Scholar · View at Scopus
  51. R. C. Levitt, M. R. McLane, D. MacDonald et al., “IL-9 pathway in asthma: new therapeutic targets for allergic inflammatory disorders,” Journal of Allergy and Clinical Immunology, vol. 103, no. 5, pp. S485–S491, 1999. View at Scopus
  52. C. Bergeron, W. Al-Ramli, and Q. Hamid, “Remodeling in asthma,” Proceedings of the American Thoracic Society, vol. 6, no. 3, pp. 301–305, 2009. View at Publisher · View at Google Scholar · View at Scopus
  53. T. Doherty and D. Broide, “Cytokines and growth factors in airway remodeling in asthma,” Current Opinion in Immunology, vol. 19, no. 6, pp. 676–680, 2007. View at Publisher · View at Google Scholar · View at Scopus
  54. J. R. Reader, D. M. Hyde, E. S. Schelegle et al., “Interleukin-9 induces mucous cell metaplasia independent of inflammation,” American Journal of Respiratory Cell and Molecular Biology, vol. 28, no. 6, pp. 664–672, 2003. View at Publisher · View at Google Scholar · View at Scopus
  55. P. D. Vermeer, R. Harson, L. A. Einwalter, T. Moninger, and J. Zabner, “Interleukin-9 induces goblet cell hyperplasia during repair of human airway epithelia,” American Journal of Respiratory Cell and Molecular Biology, vol. 28, no. 3, pp. 286–295, 2003. View at Publisher · View at Google Scholar · View at Scopus
  56. L. Whittaker, N. Niu, U.-A. Temann et al., “Interleukin-13 mediates a fundamental pathway for airway epithelial mucus induced by CD4 T cells and interleukin-9,” American Journal of Respiratory Cell and Molecular Biology, vol. 27, no. 5, pp. 593–602, 2002. View at Scopus
  57. V. Steenwinckel, J. Louahed, C. Orabona et al., “IL-13 mediates in vivo IL-9 activities on lung epithelial cells but not on hematopoietic cells,” Journal of Immunology, vol. 178, no. 5, pp. 3244–3251, 2007. View at Scopus
  58. S. Van Den Brûle, J. Heymans, X. Havaux et al., “Profibrotic effect of IL-9 overexpression in a model of airway remodeling,” American Journal of Respiratory Cell and Molecular Biology, vol. 37, no. 2, pp. 202–209, 2007. View at Publisher · View at Google Scholar · View at Scopus
  59. T. A. Doherty, P. Soroosh, D. H. Broide, and M. Croft, “CD4+ cells are required for chronic eosinophilic lung inflammation but not airway remodeling,” American Journal of Physiology, vol. 296, no. 2, pp. L229–L235, 2009. View at Publisher · View at Google Scholar · View at Scopus
  60. C. B. Boxall, S. T. Holgate, and D. E. Davies, “The contribution of transforming growth factor-β and epidermal growth factor signalling to airway remodelling in chronic asthma,” European Respiratory Journal, vol. 27, no. 1, pp. 208–229, 2006. View at Publisher · View at Google Scholar · View at Scopus
  61. C. A. Murphy, C. L. Langrish, Y. Chen et al., “Divergent Pro- and antiinflammatory roles for IL-23 and IL-12 in joint autoimmune inflammation,” Journal of Experimental Medicine, vol. 198, no. 12, pp. 1951–1957, 2003. View at Publisher · View at Google Scholar · View at Scopus
  62. D. J. Cua, J. Sherlock, Y. Chen et al., “Interleukin-23 rather than interleukin-12 is the critical cytokine for autoimmune inflammation of the brain,” Nature, vol. 421, no. 6924, pp. 744–748, 2003. View at Publisher · View at Google Scholar · View at Scopus
  63. C. L. Langrish, Y. Chen, W. M. Blumenschein et al., “IL-23 drives a pathogenic T cell population that induces autoimmune inflammation,” Journal of Experimental Medicine, vol. 201, no. 2, pp. 233–240, 2005. View at Publisher · View at Google Scholar · View at Scopus
  64. L. Steinman, “A brief history of TH17 , the first major revision in the TH1-TH2 hypothesis of T cell-mediated tissue damage,” Nature Medicine, vol. 13, no. 2, pp. 139–145, 2007. View at Publisher · View at Google Scholar · View at Scopus
  65. K. Kreymborg, R. Etzensperger, L. Dumoutier et al., “IL-22 is expressed by Th17 cells in an IL-23-dependent fashion, but not required for the development of autoimmune encephalomyelitis,” Journal of Immunology, vol. 179, no. 12, pp. 8098–8104, 2007. View at Scopus
  66. C. K. Wong, C. Y. Ho, F. W. S. Ko et al., “Proinflammatory cytokines (IL-17, IL-6, IL-18 and IL-12) and Th cytokines (IFN-γ, IL-4, IL-10 and IL-13) in patients with allergic asthma,” Clinical and Experimental Immunology, vol. 125, no. 2, pp. 177–183, 2001. View at Publisher · View at Google Scholar · View at Scopus
  67. S. Molet, Q. Hamid, F. Davoine et al., “IL-17 is increased in asthmatic airways and induces human bronchial fibroblasts to produce cytokines,” Journal of Allergy and Clinical Immunology, vol. 108, no. 3, pp. 430–438, 2001. View at Publisher · View at Google Scholar · View at Scopus
  68. J. Pène, S. Chevalier, L. Preisser et al., “Chronically inflamed human tissues are infiltrated by highly differentiated Th17 lymphocytes,” Journal of Immunology, vol. 180, no. 11, pp. 7423–7430, 2008. View at Scopus
  69. D. M. A. Bullens, E. Truyen, L. Coteur et al., “IL-17 mRNA in sputum of asthmatic patients: linking T cell driven inflammation and granulocytic influx?” Respiratory Research, vol. 7, article no. 135, 2006. View at Publisher · View at Google Scholar · View at Scopus
  70. M. Laan, Z.-H. Cui, H. Hoshino et al., “Neutrophil recruitment by human IL-17 via C-X-C chemokine release in the airways,” Journal of Immunology, vol. 162, no. 4, pp. 2347–2352, 1999. View at Scopus
  71. M. Laan, J. Lötvall, K. F. Chung, and A. Lindén, “IL-17-induced cytokine release in human bronchial epithelial cells in vitro: role of mitogen-activated protein (MAP) kinases,” British Journal of Pharmacology, vol. 133, no. 1, pp. 200–206, 2001. View at Scopus
  72. C. E. Jones and K. Chan, “Interleukin-17 stimulates the expression of interleukin-8, growth-related oncogene-α, and granulocyte-colony-stimulating factor by human airway epithelial cells,” American Journal of Respiratory Cell and Molecular Biology, vol. 26, no. 6, pp. 748–753, 2002. View at Scopus
  73. M. Kawaguchi, F. Kokubu, H. Kuga et al., “Modulation of bronchial epithelial cells by IL-17,” Journal of Allergy and Clinical Immunology, vol. 108, no. 5, pp. 804–809, 2001. View at Publisher · View at Google Scholar · View at Scopus
  74. M. Kawaguchi, F. Kokubu, M. Odaka et al., “Induction of granulocyte-macrophage colony-stimulating factor by a new cytokine, ML-1 (IL-17F), via Raf I-MEK-ERK pathway,” Journal of Allergy and Clinical Immunology, vol. 114, no. 2, pp. 444–450, 2004. View at Publisher · View at Google Scholar · View at Scopus
  75. S. Henness, C. K. Johnson, Q. Ge, C. L. Armour, J. M. Hughes, and A. J. Ammit, “IL-17A augments TNF-α-induced IL-6 expression in airway smooth muscle by enhancing mRNA stability,” Journal of Allergy and Clinical Immunology, vol. 114, no. 4, pp. 958–964, 2004. View at Publisher · View at Google Scholar · View at Scopus
  76. H. Hoshino, M. Laan, M. Sjöstrand, J. Lötvall, B.-E. Skoogh, and A. Lindén, “Increased elastase and myeloperoxidase activity associated with neutrophil recruitment by IL-17 in airways in vivo,” Journal of Allergy and Clinical Immunology, vol. 105, no. 1, pp. 143–149, 2000. View at Scopus
  77. S. L. Traves and L. E. Donnelly, “Th17 cells in airway diseases,” Current Molecular Medicine, vol. 8, no. 5, pp. 416–426, 2008. View at Publisher · View at Google Scholar · View at Scopus
  78. S. H. Gavett, X. Chen, F. Finkelman, and M. Wills-Karp, “Depletion of murine CD4+ T lymphocytes prevents antigen-induced airway hyperreactivity and pulmonary eosinophilia,” American Journal of Respiratory Cell and Molecular Biology, vol. 10, no. 6, pp. 587–593, 1994. View at Scopus
  79. P. M. Renzi, J. P. Yang, T. Diamantstein, and J. G. Martin, “Effects of depletion of cells bearing the interleukin-2 receptor on immunoglobulin production and allergic airway responses in the rat,” American Journal of Respiratory and Critical Care Medicine, vol. 153, no. 4, pp. 1214–1221, 1996. View at Scopus
  80. O. Prause, S. Bozinovski, G. P. Anderson, and A. Lindén, “Increased matrix metalloproteinase-9 concentration and activity after stimulation with interleukin-17 in mouse airways,” Thorax, vol. 59, no. 4, pp. 313–317, 2004. View at Publisher · View at Google Scholar · View at Scopus
  81. L. McKinley, J. F. Alcorn, A. Peterson et al., “TH17 cells mediate steroid-resistant airway inflammation and airway hyperresponsiveness in mice,” Journal of Immunology, vol. 181, no. 6, pp. 4089–4097, 2008. View at Scopus
  82. P. W. Hellings, A. Kasran, Z. Liu et al., “Interleukin-17 orchestrates the granulocyte influx into airways after allergen inhalation in a mouse model of allergic asthma,” American Journal of Respiratory Cell and Molecular Biology, vol. 28, no. 1, pp. 42–50, 2003. View at Publisher · View at Google Scholar · View at Scopus
  83. N. Oda, P. B. Canelos, D. M. Essayan, B. A. Plunkett, A. C. Myers, and S.-K. Huang, “Interleukin-17F induces pulmonary neutrophilia and amplifies antigen-induced allergic response,” American Journal of Respiratory and Critical Care Medicine, vol. 171, no. 1, pp. 12–18, 2005. View at Publisher · View at Google Scholar · View at Scopus
  84. J. Chakir, J. Shannon, S. Molet et al., “Airway remodeling-associated mediators in moderate to severe asthma: effect of steroids on TGF-β, IL-11, IL-17, and type I and type III collagen expression,” Journal of Allergy and Clinical Immunology, vol. 111, no. 6, pp. 1293–1298, 2003. View at Publisher · View at Google Scholar · View at Scopus
  85. C. K. Wong, S. W. M. Lun, F. W. S. Ko et al., “Activation of peripheral Th17 lymphocytes in patients with asthma,” Immunological Investigations, vol. 38, no. 7, pp. 652–664, 2009. View at Publisher · View at Google Scholar · View at Scopus
  86. Y. Zhao, J. Yang, Y.-D. Gao, and W. Guo, “Th17 immunity in patients with allergic asthma,” International Archives of Allergy and Immunology, vol. 151, no. 4, pp. 297–307, 2009. View at Publisher · View at Google Scholar · View at Scopus
  87. L. Cosmi, L. Maggi, V. Santarlasci et al., “Identification of a novel subset of human circulating memory CD4+ T cells that produce both IL-17A and IL-4,” Journal of Allergy and Clinical Immunology, vol. 125, no. 1, pp. 222–230.e4, 2010. View at Publisher · View at Google Scholar · View at Scopus
  88. C. T. Weaver, R. D. Hatton, P. R. Mangan, and L. E. Harrington, “IL-17 family cytokines and the expanding diversity of effector T cell lineages,” Annual Review of Immunology, vol. 25, pp. 821–852, 2007. View at Publisher · View at Google Scholar · View at Scopus
  89. C. Song, L. Luo, Z. Lei et al., “IL-17-producing alveolar macrophages mediate allergic lung inflammation related to asthma,” Journal of Immunology, vol. 181, no. 9, pp. 6117–6124, 2008. View at Scopus
  90. K. I. Happel, M. Zheng, E. Young et al., “Cutting edge: roles of toll-like receptor 4 and IL-23 in IL-17 expression in response to Klebsiella pneumoniae infection,” Journal of Immunology, vol. 170, no. 9, pp. 4432–4436, 2003. View at Scopus
  91. S. Ferretti, O. Bonneau, G. R. Dubois, C. E. Jones, and A. Trifilieff, “Il-17, produced by lymphocytes and neutrophils, is necessary for lipopolysaccharide-induced airway neutrophilia: IL-15 as a possible trigger,” Journal of Immunology, vol. 170, no. 4, pp. 2106–2112, 2003. View at Scopus
  92. M. A. Stark, Y. Huo, T. L. Burcin, M. A. Morris, T. S. Olson, and K. Ley, “Phagocytosis of apoptotic neutrophils regulates granulopoiesis via IL-23 and IL-17,” Immunity, vol. 22, no. 3, pp. 285–294, 2005. View at Publisher · View at Google Scholar · View at Scopus
  93. M. Pichavant, S. Goya, E. H. Meyer et al., “Ozone exposure in a mouse model induces airway hyperreactivity that requires the presence of natural killer T cells and IL-17,” Journal of Experimental Medicine, vol. 205, no. 2, pp. 385–393, 2008. View at Publisher · View at Google Scholar · View at Scopus
  94. A. Doganci, K. Sauer, R. Karwot, and S. Finotto, “Pathological role of IL-6 in the experimental allergic bronchial asthma in mice,” Clinical Reviews in Allergy and Immunology, vol. 28, no. 3, pp. 257–269, 2005. View at Publisher · View at Google Scholar · View at Scopus
  95. S. Mukhopadhyay, J. R. Hoidal, and T. K. Mukherjee, “Role of TNFα in pulmonary pathophysiology,” Respiratory Research, vol. 7, article no. 125, 2006. View at Publisher · View at Google Scholar · View at Scopus
  96. C. Brightling, M. Berry, and Y. Amrani, “Targeting TNF-α: a novel therapeutic approach for asthma,” Journal of Allergy and Clinical Immunology, vol. 121, no. 1, pp. 5–10, 2008. View at Publisher · View at Google Scholar · View at Scopus
  97. S. G. Hymowitz, E. H. Filvaroff, J. Yin et al., “IL-17s adopt a cystine knot fold: structure and activity of a novel cytokine, IL-17F, and implications for receptor binding,” EMBO Journal, vol. 20, no. 19, pp. 5332–5341, 2001. View at Publisher · View at Google Scholar · View at Scopus
  98. T. Starnes, M. J. Robertson, G. Sledge et al., “Cutting edge: IL-17F, a novel cytokine selectively expressed in activated T cells and monocytes, regulates angiogenesis and endothelial cell cytokine production,” Journal of Immunology, vol. 167, no. 8, pp. 4137–4140, 2001. View at Scopus
  99. M. Kawaguchi, F. Kokubu, S. Matsukura et al., “Induction of C-X-C chemokines, growth-related oncogene α expression, and epithelial cell-derived neutrophil-activating protein-78 by ML-1 (interleukin-17F) involves activation of raf1-mitogen-activated protein kinase kinase-extracellular signal-regulated kinase 1/2 pathway,” Journal of Pharmacology and Experimental Therapeutics, vol. 307, no. 3, pp. 1213–1220, 2003. View at Publisher · View at Google Scholar · View at Scopus
  100. M. Kawaguchi, L. F. Onuchic, X.-D. Li et al., “Identification of a novel cytokine, ML-1, and its expression in subjects with asthma,” Journal of Immunology, vol. 167, no. 8, pp. 4430–4435, 2001. View at Scopus
  101. A. L. Wurster, V. L. Rodgers, A. R. Satoskar et al., “Interleukin 21 is a T helper (Th) cell 2 cytokine that specifically inhibits the differentiation of naive Th cells into interferon γ-producing Th1 cells,” Journal of Experimental Medicine, vol. 196, no. 7, pp. 969–977, 2002. View at Publisher · View at Google Scholar · View at Scopus
  102. C. G. Vinuesa, S. G. Tangye, B. Moser, and C. R. Mackay, “Follicular B helper T cells in antibody responses and autoimmunity,” Nature Reviews Immunology, vol. 5, no. 11, pp. 853–865, 2005. View at Publisher · View at Google Scholar · View at Scopus
  103. T. Korn, E. Bettelli, W. Gao et al., “IL-21 initiates an alternative pathway to induce proinflammatory TH17 cells,” Nature, vol. 448, no. 7152, pp. 484–487, 2007. View at Publisher · View at Google Scholar · View at Scopus
  104. R. Nurieva, X. O. Yang, G. Martinez et al., “Essential autocrine regulation by IL-21 in the generation of inflammatory T cells,” Nature, vol. 448, no. 7152, pp. 480–483, 2007. View at Publisher · View at Google Scholar · View at Scopus
  105. A. Suto, D. Kashiwakuma, S.-I. Kagami et al., “Development and characterization of IL-21-producing CD4+ T cells,” Journal of Experimental Medicine, vol. 205, no. 6, pp. 1369–1379, 2008. View at Publisher · View at Google Scholar · View at Scopus
  106. L. Zhou, I. I. Ivanov, R. Spolski et al., “IL-6 programs TH-17 cell differentiation by promoting sequential engagement of the IL-21 and IL-23 pathways,” Nature Immunology, vol. 8, no. 9, pp. 967–974, 2007. View at Publisher · View at Google Scholar · View at Scopus
  107. D. T. Avery, C. S. Ma, V. L. Bryant et al., “STAT3 is required for IL-21 induced secretion of IgE from human naive B cells,” Blood, vol. 112, no. 5, pp. 1784–1793, 2008. View at Publisher · View at Google Scholar · View at Scopus
  108. K. Wolk, S. Kunz, K. Asadullah, and R. Sabat, “Cutting edge: immune cells as sources and targets of the IL-10 family members?” Journal of Immunology, vol. 168, no. 11, pp. 5397–5402, 2002. View at Scopus
  109. K. Wolk, S. Kunz, E. Witte, M. Friedrich, K. Asadullah, and R. Sabat, “IL-22 increases the innate immunity of tissues,” Immunity, vol. 21, no. 2, pp. 241–254, 2004. View at Publisher · View at Google Scholar · View at Scopus
  110. S. J. Aujla, Y. R. Chan, M. Zheng et al., “IL-22 mediates mucosal host defense against Gram-negative bacterial pneumonia,” Nature Medicine, vol. 14, no. 3, pp. 275–281, 2008. View at Publisher · View at Google Scholar · View at Scopus
  111. Y. Zheng, P. A. Valdez, D. M. Danilenko et al., “Interleukin-22 mediates early host defense against attaching and effacing bacterial pathogens,” Nature Medicine, vol. 14, no. 3, pp. 282–289, 2008. View at Publisher · View at Google Scholar · View at Scopus
  112. T. Duhen, R. Geiger, D. Jarrossay, A. Lanzavecchia, and F. Sallusto, “Production of interleukin 22 but not interleukin 17 by a subset of human skin-homing memory T cells,” Nature Immunology, vol. 10, no. 8, pp. 857–863, 2009. View at Publisher · View at Google Scholar · View at Scopus
  113. A. Knappe, S. Hör, S. Wittmann, and H. Fickenscher, “Induction of a novel cellular homolog of interleukin-10, AK155, by transformation of T lymphocytes with herpesvirus saimiri,” Journal of Virology, vol. 74, no. 8, pp. 3881–3887, 2000. View at Publisher · View at Google Scholar · View at Scopus
  114. H. Wakashin, K. Hirose, Y. Maezawa et al., “IL-23 and Th17 cells enhance Th2-cell-mediated eosinophilic airway inflammation in mice,” American Journal of Respiratory and Critical Care Medicine, vol. 178, no. 10, pp. 1023–1032, 2008. View at Publisher · View at Google Scholar · View at Scopus
  115. P. F. Y. Cheung, C. K. Wong, and C. W. K. Lam, “Molecular mechanisms of cytokine and chemokine release from eosinophils activated by IL-17A, IL-17F, and IL-23: implication for Th17 lymphocytes-mediated allergic inflammation,” Journal of Immunology, vol. 180, no. 8, pp. 5625–5635, 2008. View at Scopus
  116. C. M. Tato, A. Laurence, and J. J. O'Shea, “Helper T cell differentiation enters a new era: le roi est mort; vive le roi!,” Journal of Experimental Medicine, vol. 203, no. 4, pp. 809–812, 2006. View at Publisher · View at Google Scholar · View at Scopus
  117. G. Pan, D. French, W. Mao et al., “Forced expression of murine IL-17E induces growth retardation, jaundice, a Th2-biased response, and multiorgan inflammation in mice,” Journal of Immunology, vol. 167, no. 11, pp. 6559–6567, 2001. View at Scopus
  118. M. R. Kim, R. Manoukian, R. Yeh et al., “Transgenic overexpression of human IL-17E results in eosinophilia, B-lymphocyte hyperplasia, and altered antibody production,” Blood, vol. 100, no. 7, pp. 2330–2340, 2002. View at Publisher · View at Google Scholar · View at Scopus
  119. S. D. Hurst, T. Muchamuel, D. M. Gorman et al., “New IL-17 family members promote Th1 or Th2 responses in the lung: in vivo function of the novel cytokine IL-25,” Journal of Immunology, vol. 169, no. 1, pp. 443–453, 2002. View at Scopus
  120. A. M. Owyang, C. Zaph, E. H. Wilson et al., “Interleukin 25 regulates type 2 cytokine-dependent immunity and limits chronic inflammation in the gastrointestinal tract,” Journal of Experimental Medicine, vol. 203, no. 4, pp. 843–849, 2006. View at Publisher · View at Google Scholar · View at Scopus
  121. P. G. Fallon, S. J. Ballantyne, N. E. Mangan et al., “Identification of an interleukin (IL)-25-dependent cell population that provides IL-4, IL-5, and IL-13 at the onset of helminth expulsion,” Journal of Experimental Medicine, vol. 203, no. 4, pp. 1105–1116, 2006. View at Publisher · View at Google Scholar · View at Scopus
  122. S. J. Ballantyne, J. L. Barlow, H. E. Jolin et al., “Blocking IL-25 prevents airway hyperresponsiveness in allergic asthma,” Journal of Allergy and Clinical Immunology, vol. 120, no. 6, pp. 1324–1331, 2007. View at Publisher · View at Google Scholar · View at Scopus
  123. T. Tamachi, Y. Maezawa, K. Ikeda et al., “IL-25 enhances allergic airway inflammation by amplifying a TH2 cell-dependent pathway in mice,” Journal of Allergy and Clinical Immunology, vol. 118, no. 3, pp. 606–614, 2006. View at Publisher · View at Google Scholar · View at Scopus
  124. P. Stock, V. Lombardi, V. Kohlrautz, and O. Akbari, “Induction of airway hyperreactivity by IL-25 is dependent on a subset of invariant NKT cells expressing IL-17RB,” Journal of Immunology, vol. 182, no. 8, pp. 5116–5122, 2009. View at Publisher · View at Google Scholar · View at Scopus
  125. P. Angkasekwinai, S. H. Chang, M. Thapa, H. Watarai, and C. Dong, “Regulation of IL-9 expression by IL-25 signaling,” Nature Immunology, vol. 11, no. 3, pp. 250–256, 2010. View at Publisher · View at Google Scholar · View at Scopus
  126. D. E. Smith, “IL-33: a tissue derived cytokine pathway involved in allergic inflammation and asthma,” Clinical and Experimental Allergy, vol. 40, no. 2, pp. 200–208, 2010. View at Publisher · View at Google Scholar · View at Scopus
  127. F. Y. Liew, N. I. Pitman, and I. B. McInnes, “Disease-associated functions of IL-33: the new kid in the IL-1 family,” Nature Reviews in Immunology, vol. 10, no. 2, pp. 103–110, 2010.
  128. S. Sakaguchi, M. Ono, R. Setoguchi et al., “Foxp3+CD25+CD4+ natural regulatory T cells in dominant self-tolerance and autoimmune disease,” Immunological Reviews, vol. 212, pp. 8–27, 2006. View at Publisher · View at Google Scholar · View at Scopus
  129. C. A. Akdis and M. Akdis, “Mechanisms and treatment of allergic disease in the big picture of regulatory T cells,” Journal of Allergy and Clinical Immunology, vol. 123, no. 4, pp. 735–746, 2009. View at Publisher · View at Google Scholar · View at Scopus
  130. D. S. Robinson, “Regulatory T cells and asthma,” Clinical and Experimental Allergy, vol. 39, no. 9, pp. 1314–1323, 2009. View at Publisher · View at Google Scholar · View at Scopus
  131. E. M. Ling, T. Smith, X. D. Nguyen et al., “Relation of CD4+CD25+ regulatory T-cell suppression of allergen-driven T-cell activation to atopic status and expression of allergic disease,” Lancet, vol. 363, no. 9409, pp. 608–615, 2004. View at Publisher · View at Google Scholar · View at Scopus
  132. K. Presser, D. Schwinge, M. Wegmann et al., “Coexpression of TGF-beta1 and IL-10 enables regulatory T cells to completely suppress airway hyperreactivity,” Journal of Immunology, vol. 181, no. 11, pp. 7751–7758, 2008. View at Scopus
  133. H. Grindebacke, K. Wing, A. C. Andersson, E. Suri-Payer, S. Rak, and A. Rudin, “Defective suppression of Th2 cytokines by CD4CD25 regulatory T cells in birch allergics during birch pollen season,” Clinical Experimental Allergy, vol. 34, no. 9, pp. 1364–1372, 2004.
  134. M. Akdis, J. Verhagen, A. Taylor et al., “Immune responses in healthy and allergic individuals are characterized by a fine balance between allergen-specific T regulatory 1 and T helper 2 cells,” Journal of Experimental Medicine, vol. 199, no. 11, pp. 1567–1575, 2004. View at Publisher · View at Google Scholar · View at Scopus
  135. D. Hartl, B. Koller, A. T. Mehlhorn et al., “Quantitative and functional impairment of pulmonary CD4+CD25hi regulatory T cells inpediatric asthma,” Journal of Allergy and Clinical Immunology, vol. 119, no. 5, pp. 1258–1266, 2007. View at Publisher · View at Google Scholar · View at Scopus
  136. Y.-L. Lin, C.-C. Shieh, and J.-Y. Wang, “The functional insufficiency of human CD4+CD25high T-regulatory cells in allergic asthma is subjected to TNF-α modulation,” Allergy, vol. 63, no. 1, pp. 67–74, 2008. View at Publisher · View at Google Scholar · View at Scopus
  137. K. D. Nguyen, A. Fohner, J. D. Booker, C. Dong, A. M. Krensky, and K. C. Nadeau, “XCL1 enhances regulatory activities of CD4+CD25highCD127low/- T cells in human allergic asthma,” Journal of Immunology, vol. 181, no. 8, pp. 5386–5395, 2008. View at Scopus
  138. K. D. Nguyen, C. Vanichsarn, A. Fohner, and K. C. Nadeau, “Selective deregulation in chemokine signaling pathways of CD4+CD25hiCD127lo/- regulatory T cells in human allergic asthma,” Journal of Allergy and Clinical Immunology, vol. 123, no. 4, pp. 933–939, 2009. View at Publisher · View at Google Scholar · View at Scopus
  139. X. O. Yang, R. Nurieva, G. J. Martinez et al., “Molecular antagonism and plasticity of regulatory and inflammatory T cell programs,” Immunity, vol. 29, no. 1, pp. 44–56, 2008. View at Publisher · View at Google Scholar · View at Scopus
  140. L. Xu, A. Kitani, I. Fuss, and W. Strober, “Cutting edge: regulatory T cells induce CD4+CD25 -Foxp3- T cells or are self-induced to become Th17 cells in the absence of exogenous TGF-β,” Journal of Immunology, vol. 178, no. 11, pp. 6725–6729, 2007. View at Scopus
  141. M. Lochner, L. Peduto, M. Cherrier, et al., “In vivo equilibrium of proinflammatory IL-17+ and regulatory IL-10+ Foxp3+ RORgamma t+ T cells,” Journal of Experimental Medicine, vol. 205, no. 6, pp. 1381–1393, 2008.
  142. K. S. Voo, Y.-H. Wang, F. R. Santori et al., “Identification of IL-17-producing FOXP3+ regulatory T cells in humans,” Proceedings of the National Academy of Sciences of the United States of America, vol. 106, no. 12, pp. 4793–4798, 2009. View at Publisher · View at Google Scholar · View at Scopus
  143. N. Komatsu, M. E. Mariotti-Ferrandiz, Y. Wang, B. Malissen, H. Waldmann, and S. Hori, “Heterogeneity of natural Foxp3+ T cells: a committed regulatory T-cell lineage and an uncommitted minor population retaining plasticity,” Proceedings of the National Academy of Sciences of the United States of America, vol. 106, no. 6, pp. 1903–1908, 2009. View at Publisher · View at Google Scholar · View at Scopus
  144. C. King, S. G. Tangye, and C. R. Mackay, “T follicular helper (TFH) cells in normal and dysregulated immune responses,” Annual Review of Immunology, vol. 26, pp. 741–766, 2008. View at Publisher · View at Google Scholar · View at Scopus
  145. A. Vogelzang, H. M. McGuire, D. Yu, J. Sprent, C. R. Mackay, and C. King, “A fundamental role for interleukin-21 in the generation of T follicular helper cells,” Immunity, vol. 29, no. 1, pp. 127–137, 2008. View at Publisher · View at Google Scholar · View at Scopus
  146. R. I. Nurieva, Y. Chung, D. Hwang et al., “Generation of T follicular helper cells is mediated by interleukin-21 but independent of T helper 1, 2, or 17 cell lineages,” Immunity, vol. 29, no. 1, pp. 138–149, 2008. View at Publisher · View at Google Scholar · View at Scopus
  147. M. Tsuji, N. Komatsu, S. Kawamoto et al., “Preferential generation of follicular B helper T cells from Foxp3+ T cells in gut Peyer's patches,” Science, vol. 323, no. 5920, pp. 1488–1492, 2009. View at Publisher · View at Google Scholar · View at Scopus
  148. K. M. Ansel, I. Djuretic, B. Tanasa, and A. Rao, “Regulation of Th2 differentiation and Il4 locus accessibility,” Annual Review of Immunology, vol. 24, pp. 607–656, 2006. View at Publisher · View at Google Scholar · View at Scopus
  149. S. J. Szabo, B. M. Sullivan, S. L. Peng, and L. H. Glimcher, “Molecular mechanisms regulating Th1 immune responses,” Annual Review of Immunology, vol. 21, pp. 713–758, 2003. View at Publisher · View at Google Scholar · View at Scopus
  150. T. Shirakawa, T. Enomoto, S.-I. Shimazu, and J. M. Hopkin, “The inverse association between tuberculin responses and atopic disorder,” Science, vol. 275, no. 5296, pp. 77–79, 1997. View at Publisher · View at Google Scholar · View at Scopus
  151. L. Tang, S. Benjaponpitak, R. H. DeKruyff, and D. T. Umetsu, “Reduced prevalence of allergic disease in patients with multiple sclerosis is associated with enhanced IL-12 production,” Journal of Allergy and Clinical Immunology, vol. 102, no. 3, pp. 428–435, 1998. View at Publisher · View at Google Scholar · View at Scopus
  152. J. I. Székely and A. Pataki, “Recent findings on the pathogenesis of bronchial asthma—part II. The role of hormonal predisposition, environmental influences and conditioning leading to bronchial asthma,” Acta Physiologica Hungarica, vol. 96, no. 3, pp. 289–305, 2009. View at Publisher · View at Google Scholar · View at Scopus
  153. D. A. Kuperman, X. Huang, L. L. Koth et al., “Direct effects of interleukin-13 on epithelial cells cause airway hyperreactivity and mucus overproduction in asthma,” Nature Medicine, vol. 8, no. 8, pp. 885–889, 2002. View at Publisher · View at Google Scholar · View at Scopus
  154. A. Nakanishi, S. Morita, H. Iwashita et al., “Role of gob-5 in mucus overproduction and airway hyperresponsiveness in asthma,” Proceedings of the National Academy of Sciences of the United States of America, vol. 98, no. 9, pp. 5175–5180, 2001. View at Publisher · View at Google Scholar · View at Scopus
  155. A. K. Abbas, K. M. Murphy, and A. Sher, “Functional diversity of helper T lymphocytes,” Nature, vol. 383, no. 6603, pp. 787–793, 1996. View at Publisher · View at Google Scholar · View at Scopus
  156. S. H. Gavett, D. J. O'Hearn, X. Li, S.-K. Huang, F. D. Finkelman, and M. Wills-Karp, “Interleukin 12 inhibits antigen-induced airway hyperresponsiveness, inflammation, and Th2 cytokine expression in mice,” Journal of Experimental Medicine, vol. 182, no. 5, pp. 1527–1536, 1995. View at Publisher · View at Google Scholar · View at Scopus
  157. C. L. Hofstra, I. Van Ark, G. Hofman, M. Kool, F. P. Nijkamp, and A. J. M. Van Oosterhout, “Prevention of Th2-like cell responses by coadministration of IL-12 and IL-18 is associated with inhibition of antigen-induced airway hyperresponsiveness, eosinophilia, and serum IgE levels,” Journal of Immunology, vol. 161, no. 9, pp. 5054–5060, 1998. View at Scopus
  158. V. P. Yeung, R. S. Gieni, D. T. Umetsu, and R. H. DeKruyff, “Heat-killed Listeria monocytogenes as an adjuvant converts established murine Th2-dominated immune responses into Th1-dominated responses,” Journal of Immunology, vol. 161, no. 8, pp. 4146–4152, 1998. View at Scopus
  159. T.-J. Huang, P. A. MacAry, P. Eynott et al., “Allergen-specific Th1 cells counteract efferent Th2 cell-dependent bronchial hyperresponsiveness and eosinophilic inflammation partly via IFN-γ,” Journal of Immunology, vol. 166, no. 1, pp. 207–217, 2001. View at Scopus
  160. K. J. Bodey, A. E. Semper, A. E. Redington et al., “Cytokine profiles of BAL T cells and T-cell clones obtained from human asthmatic airways after local allergen challenge,” Allergy, vol. 54, no. 10, pp. 1083–1093, 1999. View at Publisher · View at Google Scholar · View at Scopus
  161. A. C. Mullen, F. A. High, A. S. Hutchins et al., “Role of T-bet in commitment of TH1 cells before IL- 12-dependent selection,” Science, vol. 292, no. 5523, pp. 1907–1910, 2001. View at Publisher · View at Google Scholar · View at Scopus
  162. M. Afkarian, J. R. Sedy, J. Yang, et al., “T-bet is a STAT1-induced regulator of IL-12R expression in naïve CD4+ Tcells,” Nature Immunology, vol. 3, no. 6, pp. 549–557, 2002.
  163. L. Cohn, J. S. Tepper, and K. Bottomly, “Cutting edge: IL-4-independent induction of airway hyperresponsiveness by Th2, but not Th1, cells,” Journal of Immunology, vol. 161, no. 8, pp. 3813–3816, 1998. View at Scopus
  164. G. Hansen, G. Berry, R. H. DeKruyff, and D. T. Umetsu, “Allergen-specific Th1 cells fail to counterbalance Th2 cell-induced airway hyperreactivity but cause severe airway inflammation,” Journal of Clinical Investigation, vol. 103, no. 2, pp. 175–183, 1999. View at Scopus
  165. E. Sawicka, C. Zuany-Amorim, C. Manlius et al., “Inhibition of Th1- and Th2-mediated airway inflammation by the sphingosine 1-phosphate receptor agonist FTY720,” Journal of Immunology, vol. 171, no. 11, pp. 6206–6214, 2003. View at Scopus
  166. J. Cui, S. Pazdziorko, J. S. Miyashiro et al., “TH1-mediated airway hyperresponsiveness independent of neutrophilic inflammation,” Journal of Allergy and Clinical Immunology, vol. 115, no. 2, pp. 309–315, 2005. View at Publisher · View at Google Scholar · View at Scopus
  167. J. G. Ford, D. Rennick, D. D. Donaldson et al., “IL-13 and IFN-γ: interactions in lung inflammation,” Journal of Immunology, vol. 167, no. 3, pp. 1769–1777, 2001. View at Scopus
  168. D. A. Randolph, C. J. L. Carruthers, S. J. Szabo, K. M. Murphy, and D. D. Chaplin, “Modulation of airway inflammation by passive transfer of allergen-specific Th1 and Th2 cells in a mouse model of asthma,” Journal of Immunology, vol. 162, no. 4, pp. 2375–2383, 1999. View at Scopus
  169. N. Krug, J. Madden, A. E. Redington et al., “T-cell cytokine profile evaluated at the single cell level in BAL and blood in allergic asthma,” American Journal of Respiratory Cell and Molecular Biology, vol. 14, no. 4, pp. 319–326, 1996. View at Scopus
  170. M. J. Holtzman, D. Sampath, M. Castro, D. C. Look, and S. Jayaraman, “The one-two of T helper cells: does interferon-γ knock out the Th2 hypothesis for asthma?” American Journal of Respiratory Cell and Molecular Biology, vol. 14, no. 4, pp. 316–318, 1996. View at Scopus
  171. B. E. Hol, B. Bruinier, R. Lutter, H. M. Jansen, and T. A. Out, “Cytokine production by T-cell clones from bronchoalveolar lavage fluid of patients with asthma and healthy subjects,” European Respiratory Journal, vol. 9, no. 22, supplement, pp. 95s–103s, 1996. View at Scopus
  172. H. Okamura, H. Tsutsui, T. Komatsu et al., “Cloning of a new cytokine that induces IFN-γ production by T cells,” Nature, vol. 378, no. 6552, pp. 88–91, 1995. View at Publisher · View at Google Scholar · View at Scopus
  173. L. A. Cameron, R. A. Taha, A. Tsicopoulos et al., “Airway epithelium expresses interleukin-18,” European Respiratory Journal, vol. 14, no. 3, pp. 553–559, 1999. View at Publisher · View at Google Scholar · View at Scopus
  174. T. Yoshimoto, K. Takeda, T. Tanaka et al., “IL-12 up-regulates IL-18 receptor expression on T cells, Th1 cells, and B cells: synergism with IL-18 for IFN-γ production,” Journal of Immunology, vol. 161, no. 7, pp. 3400–3407, 1998. View at Scopus
  175. N. Hayashi, T. Yoshimoto, K. Izuhara, K. Matsui, T. Tanaka, and K. Nakanishi, “T helper 1 cells stimulated with ovalbumin and IL-18 induce airway hyperresponsiveness and lung fibrosis by IFN-γ and IL-13 production,” Proceedings of the National Academy of Sciences of the United States of America, vol. 104, no. 37, pp. 14765–14770, 2007. View at Publisher · View at Google Scholar · View at Scopus
  176. T. Sugimoto, Y. Ishikawa, T. Yoshimoto, N. Hayashi, J. Fujimoto, and K. Nakanishi, “Interleukin 18 acts on memory T helper cells type 1 to induce airway inflammation and hyperresponsiveness in a naive host mouse,” Journal of Experimental Medicine, vol. 199, no. 4, pp. 535–545, 2004. View at Publisher · View at Google Scholar · View at Scopus
  177. E. Maggi, P. Parronchi, R. Manetti et al., “Reciprocal regulatory effects of IFN-γ and IL-4 on the in vitro development of human Th1 and Th2 clones,” Journal of Immunology, vol. 148, no. 7, pp. 2142–2147, 1992. View at Scopus
  178. T. Valerius, R. Repp, J. R. Kalden, and E. Platzer, “Effects of IFN on human eosinophils in comparison with other cytokines. A novel class of eosinophil activators with delayed onset of action,” Journal of Immunology, vol. 145, no. 9, pp. 2950–2958, 1990. View at Scopus
  179. D. C. Look, S. R. Rapp, B. T. Keller, and M. J. Holtzman, “Selective induction of intercellular adhesion molecule-1 by interferon-γ in human airway epithelial cells,” American Journal of Physiology, vol. 263, no. 1, pp. L79–L87, 1992. View at Scopus
  180. R. K. Kumar, D. C. Webb, C. Herbert, and P. S. Foster, “Interferon-γ as a possible target in chronic asthma,” Inflammation and Allergy, vol. 5, no. 4, pp. 253–256, 2006. View at Publisher · View at Google Scholar · View at Scopus
  181. A. Takaoka, Y. Tanaka, T. Tsuji et al., “A critical role for mouse CXC chemokine(s) in pulmonary neutrophilia during Th type 1-dependent airway inflammation,” Journal of Immunology, vol. 167, no. 4, pp. 2349–2353, 2001. View at Scopus
  182. A. Bendelac, M. N. Rivera, S.-H. Park, and J. H. Roark, “Mouse CD1-specific NK1 T cells: development, specificity, and function,” Annual Review of Immunology, vol. 15, pp. 535–562, 1997. View at Publisher · View at Google Scholar · View at Scopus
  183. M. Taniguchi, M. Harada, S. Kojo, T. Nakayama, and H. Wakao, “The regulatory role of Valpha14 NKT cells in innate and acquired immune response,” Annual Reviews of Immunology, vol. 21, pp. 483–513, 2003.
  184. M. Kronenberg, “Toward an understanding of NKT cell biology: progress and paradoxes,” Annual Review of Immunology, vol. 23, pp. 877–900, 2005. View at Publisher · View at Google Scholar · View at Scopus
  185. D. I. Godfrey, H. R. MacDonald, M. Kronenberg, M. J. Smyth, and L. Van Kaer, “NKT cells: what's in a name?” Nature Reviews Immunology, vol. 4, no. 3, pp. 231–237, 2004. View at Scopus
  186. T. Yoshimoto, A. Bendelac, C. Watson, J. Hu-Li, and W. E. Paul, “Role of NK1.1+ T cells in a TH2 response and in immunoglobulin E production,” Science, vol. 270, no. 5243, pp. 1845–1847, 1995. View at Scopus
  187. S. T. Smiley, M. H. Kaplan, and M. J. Grusby, “Immunoglobulin E production in the absence of interleukin-4-secreting CD1-dependent cells,” Science, vol. 275, no. 5302, pp. 977–979, 1997. View at Publisher · View at Google Scholar · View at Scopus
  188. O. Akbari, P. Stock, E. Meyer et al., “Essential role of NKT cells producing IL-4 and IL-13 in the development of allergen-induced airway hyperreactivity,” Nature Medicine, vol. 9, no. 5, pp. 582–588, 2003. View at Publisher · View at Google Scholar · View at Scopus
  189. Y. Sen, B. Yongyi, H. Yuling, et al., “V alpha 24-invariant NKT cells from patients with allergic asthma express CCR9 at high frequency and induce Th2 bias of CD3+ T cells upon CD226 engagement,” Journal of Immunology, vol. 175, no. 8, pp. 4914–4926, 2005.
  190. O. Akbari, J. L. Faul, E. G. Hoyte et al., “CD4+ invariant T-cell-receptor+ natural killer T cells in bronchial asthma,” New England Journal of Medicine, vol. 354, no. 11, pp. 1117–1129, 2006. View at Publisher · View at Google Scholar · View at Scopus
  191. J. M. Coquet, S. Chakravarti, K. Kyparissoudis et al., “Diverse cytokine production by NKT cell subsets and identification of an IL-17-producing CD4-NK1. 1- NKT cell population,” Proceedings of the National Academy of Sciences of the United States of America, vol. 105, no. 32, pp. 11287–11292, 2008. View at Publisher · View at Google Scholar · View at Scopus
  192. A. V. Rachitskaya, A. M. Hansen, and R. Horai, “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,” Journal of Immunology, vol. 180, no. 8, pp. 5167–5171, 2008.
  193. M. Goto, M. Murakawa, K. Kadoshima-Yamaoka et al., “Murine NKT cells produce Th17 cytokine interleukin-22,” Cellular Immunology, vol. 254, no. 2, pp. 81–84, 2009. View at Publisher · View at Google Scholar · View at Scopus