Natural Killer Cells in the Development of Asthma

  • Clinton B. Mathias
Part of the following topical collections:
  1. Topical Collection on Basic and Applied Science


Asthma is an immune-mediated disease of the airways characterized by reversible airway obstruction, bronchial eosinophilic inflammation, and airway hyperresponsiveness (AHR). The immune dysregulation in asthma has been attributed to the involvement of diverse immune cells that contribute to the immunopathology of the disease. Natural killer (NK) cells play critical roles in host defense against viruses and various cancers. Accumulating evidence demonstrates additional important roles for these cells in T cell priming, dendritic cell maturation, and the development of inflammation, all of which have the potential to enhance or dampen allergic responses. The ability of NK cells to produce Th2-type cytokines and their pivotal role in combating respiratory infections which cause airway dysfunction in asthmatics further suggest that they may directly contribute to the immunopathogenesis of allergic airway disease. In this review, we examine emerging evidence and discuss the putative roles of NK cells in the sensitization, progression, and resolution of asthma.


Natural killer cells Asthma Allergic inflammation NKG2D NK2 


Compliance with Ethics Guidelines

Conflict of Interest

Clinton B. Mathias declares no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.


Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 1.
    Walker C, Kaegi MK, Braun P, Blaser K. Activated T cells and eosinophilia in bronchoalveolar lavages from subjects with asthma correlated with disease severity. J Allergy Clin Immunol. 1991;88(6):935–42.PubMedCrossRefGoogle Scholar
  2. 2.
    Azzawi M, Johnston PW, Majumdar S, Kay AB, Jeffery PK. T lymphocytes and activated eosinophils in airway mucosa in fatal asthma and cystic fibrosis. Am Rev Respir Dis. 1992;145(6):1477–82.PubMedCrossRefGoogle Scholar
  3. 3.
    Virchow Jr JC, Walker C, Hafner D, Kortsik C, Werner P, Matthys H, et al. T cells and cytokines in bronchoalveolar lavage fluid after segmental allergen provocation in atopic asthma. Am J Respir Crit Care Med. 1995;151(4):960–8.PubMedGoogle Scholar
  4. 4.
    Wills-Karp M. Immunologic basis of antigen-induced airway hyperresponsiveness. Annu Rev Immunol. 1999;17:255–81.PubMedCrossRefGoogle Scholar
  5. 5.
    Lee NA, Gelfand EW, Lee JJ. Pulmonary T cells and eosinophils: coconspirators or independent triggers of allergic respiratory pathology? J Allergy Clin Immunol. 2001;107(6):945–57.PubMedCrossRefGoogle Scholar
  6. 6.
    Hamelmann E, Gelfand EW. IL-5-induced airway eosinophilia—the key to asthma? Immunol Rev. 2001;179:182–91.PubMedCrossRefGoogle Scholar
  7. 7.
    Oettgen HC, Geha RS. IgE regulation and roles in asthma pathogenesis. J Allergy Clin Immunol. 2001;107(3):429–40.PubMedCrossRefGoogle Scholar
  8. 8.
    Lambrecht BN, Hammad H. Taking our breath away: dendritic cells in the pathogenesis of asthma. Nat Rev Immunol. 2003;3(12):994–1003.PubMedCrossRefGoogle Scholar
  9. 9.
    Lambrecht BN, Hammad H. The other cells in asthma: dendritic cell and epithelial cell crosstalk. Curr Opin Pulm Med. 2003;9(1):34–41.PubMedCrossRefGoogle Scholar
  10. 10.
    Wills-Karp M, Chiaramonte M. Interleukin-13 in asthma. Curr Opin Pulm Med. 2003;9(1):21–7.PubMedCrossRefGoogle Scholar
  11. 11.
    Wills-Karp Marsha H. Immunological mechanisms of allergic disorders. In: Paul W, editor. Fundamental immunology. Philadelphia: Lippincott-Raven Publishers; 2003. p. 1439–79.Google Scholar
  12. 12.
    Cohn L, Elias JA, Chupp GL. Asthma: mechanisms of disease persistence and progression. Annu Rev Immunol. 2004;22:789–815.PubMedCrossRefGoogle Scholar
  13. 13.
    Wills-Karp M, Ewart SL. Time to draw breath: asthma-susceptibility genes are identified. Nat Rev Genet. 2004;5(5):376–87.PubMedCrossRefGoogle Scholar
  14. 14.
    Frieri M. Asthma concepts in the new millennium: update in asthma pathophysiology. Allergy Asthma Proc. 2005;26(2):83–8.PubMedGoogle Scholar
  15. 15.
    Frieri M. Advances in the understanding of allergic asthma. Allergy Asthma Proc. 2007;28(6):614–9. doi: 10.2500/Aap.2007.28.2952.PubMedCrossRefGoogle Scholar
  16. 16.
    Medoff BD, Thomas SY, Luster AD. T cell trafficking in allergic asthma: the ins and outs. Annu Rev Immunol. 2008;26:205–32. doi: 10.1146/Annurev.Immunol.26.021607.090312.PubMedCrossRefGoogle Scholar
  17. 17.
    Kim HY, Dekruyff RH, Umetsu DT. The many paths to asthma: phenotype shaped by innate and adaptive immunity. Nat Immunol. 2010;11(7):577–84. doi: 10.1038/Ni.1892.PubMedCentralPubMedCrossRefGoogle Scholar
  18. 18.•
    Holgate S. Innate and adaptive immune responses in asthma. Nat Med. 2012;18(5):673–83. doi: 10.1038/Nm.2731. A Recent Review Detailing The Role Of Innate And Adaptive Immune Cells In Asthma.PubMedCrossRefGoogle Scholar
  19. 19.
    Lund S, Walford HH, Doherty TA. Type 2 innate lymphoid cells in allergic disease. Curr Immunol Rev. 2013;9(4):214–21. doi: 10.2174/1573395510666140304235916.PubMedCentralPubMedCrossRefGoogle Scholar
  20. 20.
    Holtzman MJ, Byers DE, Alexander-Brett J, Wang X. The role of airway epithelial cells and innate immune cells in chronic respiratory disease. Nat Rev Immunol. 2014;14(10):686–98. doi: 10.1038/Nri3739.PubMedCrossRefGoogle Scholar
  21. 21.
    Korsgren M, Persson CG, Sundler F, Bjerke T, Hansson T, Chambers BJ, et al. Natural killer cells determine development of allergen-induced eosinophilic airway inflammation in mice. J Exp Med. 1999;189(3):553–62.PubMedCentralPubMedCrossRefGoogle Scholar
  22. 22.••
    Mathias CB, Guernsey LA, Zammit D, Brammer C, Wu C, Thrall RS, et al. Pro-inflammatory role of natural killer cells in the development of allergic airway disease. Clin Exp Allergy. 2014;44(4):589–601. doi: 10.1111/Cea.12271. This Article Demonstrates That NK Cells Are Recruited To The Allergic Airways, And That In The Absence Of NK Cells, In NK-Deficient Mice Or Mice Depleted Of NK Cell Subsets, Airway Inflammation Is Attenuated. It Also Shows That NK Cells Are Required At Priming, And That NK Cells Regulate The Number Of Dendritic Cells In Spleens And Lungs Of Allergic Mice.
  23. 23.••
    Ple C, Barrier M, Amniai L, Marquillies P, Bertout J, Tsicopoulos A, et al. Natural killer cells accumulate in lung-draining lymph nodes and regulate airway eosinophilia in a murine model of asthma. Scand J Immunol. 2010;72(2):118–27. doi: 10.1111/J.1365-3083.2010.02419.X. This Article Demonstrates That NK Cells Are Recruited To The Lung-Draining Lymph Nodes Of Allergic Mice, And That They Are Required During The Challenge Phase Of The Airway Response, As Shown By Depleting NK Cells Using The Anti-Asialo GM 1 Antibody.
  24. 24.••
    Farhadi N, Lambert L, Triulzi C, Openshaw PJ, Guerra N, Culley FJ. Natural killer cell NKG2D and granzyme B are critical for allergic pulmonary inflammation. J Allergy Clin Immunol. 2014;133(3):827–35 E3. doi: 10.1016/J.Jaci.2013.09.048. This Article Demonstrates That NKG2D-Deficient Mice Were Resistant To The Induction Of Eosinophilia And Exhibited Decreased Eosinophilia And IgE Production. Furthermore, Adoptive Transfer Of NK Cells Only Reconstituted Disease If The NK Cells Expressed GranzymeB.
  25. 25.
    Akbari O, Stock P, Meyer E, Kronenberg M, Sidobre S, Nakayama T, et al. Essential role of NKT cells producing IL-4 and IL-13 in the development of allergen-induced airway hyperreactivity. Nat Med. 2003;9(5):582–8.PubMedCrossRefGoogle Scholar
  26. 26.
    Akbari O, Faul JL, Hoyte EG, Berry GJ, Wahlstrom J, Kronenberg M, et al. CD4+ invariant T-cell-receptor+ natural killer T cells in bronchial asthma. N Engl J Med. 2006;354(11):1117–29. doi: 10.1056/Nejmoa053614.
  27. 27.
    Koh YI, Shim JU, Lee JH, Chung IJ, Min JJ, Rhee JH, et al. Natural killer T cells are dispensable in the development of allergen-induced airway hyperresponsiveness, inflammation and remodelling in a mouse model of chronic asthma. Clin Exp Immunol. 2010;161(1):159–70. doi: 10.1111/J.1365-2249.2010.04151.X.PubMedCentralPubMedGoogle Scholar
  28. 28.
    Shim JU, Koh YI. Increased Th2-like invariant natural killer T cells in peripheral blood from patients with asthma. Allergy Asthma Immunol Res. 2014;6(5):444–8. doi: 10.4168/Aair.2014.6.5.444.PubMedCentralPubMedCrossRefGoogle Scholar
  29. 29.
    Schramm CM, Puddington L, Yiamouyiannis CA, Lingenheld EG, Whiteley HE, Wolyniec WW, et al. Proinflammatory roles of T-cell receptor (TCR)gammadelta and TCRalphabeta lymphocytes in a murine model of asthma. Am J Respir Cell Mol Biol. 2000;22(2):218–25.PubMedCrossRefGoogle Scholar
  30. 30.
    Chang YJ, Kim HY, Albacker LA, Baumgarth N, Mckenzie AN, Smith DE, et al. Innate lymphoid cells mediate influenza-induced airway hyper-reactivity independently of adaptive immunity. Nat Immunol. 2011;12(7):631–8. doi: 10.1038/Ni.2045.PubMedCentralPubMedCrossRefGoogle Scholar
  31. 31.
    Kim HY, Chang YJ, Subramanian S, Lee H, Albacker LA, Matangkasombut P, et al. Innate lymphoid cells responding to IL-33 mediate airway hyperreactivity independently of adaptive immunity. J Allergy Clin Immunol. 2012;129(1):216–27 E1-6. doi: 10.1016/J.Jaci.2011.10.036.PubMedCentralPubMedCrossRefGoogle Scholar
  32. 32.
    Chang YJ, Dekruyff RH, Umetsu DT. The role of type 2 innate lymphoid cells in asthma. J Leukoc Biol. 2013;94(5):933–40. doi: 10.1189/Jlb.0313127.PubMedCrossRefGoogle Scholar
  33. 33.
    Yu S, Kim HY, Chang YJ, Dekruyff RH, Umetsu DT. Innate lymphoid cells and asthma. J Allergy Clin Immunol. 2014;133(4):943–50. doi: 10.1016/J.Jaci.2014.02.015.
  34. 34.
    Biron CA. Activation and function of natural killer cell responses during viral infections. Curr Opin Immunol. 1997;9(1):24–34.PubMedCrossRefGoogle Scholar
  35. 35.
    Yokoyama WM, Kim S, French AR. The dynamic life of natural killer cells. Annu Rev Immunol. 2004;22:405–29.PubMedCrossRefGoogle Scholar
  36. 36.•
    Cooper MA, Colonna M, Yokoyama WM. Hidden talents of natural killers: NK cells in innate and adaptive immunity. EMBO Rep. 2009;10(10):1103–10. doi: 10.1038/Embor.2009.203. This Important Review Details The Role Of NK Cells In Various Innate And Adaptive Immune Responses.
  37. 37.
    Natarajan K, Dimasi N, Wang J, Mariuzza RA, Margulies DH. Structure and function of natural killer cell receptors: multiple molecular solutions to self, nonself discrimination. Annu Rev Immunol. 2002;20:853–85.PubMedCrossRefGoogle Scholar
  38. 38.
    Raulet DH. Natural killer cells. In: Paul WE, editor. Fundamental immunology. Philadelphia: Lippincott-Raven Publishers; 2003. p. 365–91.Google Scholar
  39. 39.
    Cooper MA, Fehniger TA, Caligiuri MA. The biology of human natural killer-cell subsets. Trends Immunol. 2001;22(11):633–40.PubMedCrossRefGoogle Scholar
  40. 40.
    Colucci F, Caligiuri MA, Di Santo JP. What does it take to make a natural killer? Nat Rev Immunol. 2003;3(5):413–25.PubMedCrossRefGoogle Scholar
  41. 41.
    Di Santo JP. Functionally distinct NK-cell subsets: developmental origins and biological implications. Eur J Immunol. 2008;38(11):2948–51. doi: 10.1002/Eji.200838830.PubMedCrossRefGoogle Scholar
  42. 42.
    Fehniger TA, Caligiuri MA. Interleukin 15: biology and relevance to human disease. Blood. 2001;97(1):14–32.PubMedCrossRefGoogle Scholar
  43. 43.
    Dokun AO, Kim S, Smith HR, Kang HS, Chu DT, Yokoyama WM. Specific and nonspecific NK cell activation during virus infection. Nat Immunol. 2001;2(10):951–6.PubMedCrossRefGoogle Scholar
  44. 44.
    Koka R, Burkett PR, Chien M, Chai S, Chan F, Lodolce JP, et al. Interleukin (IL)-15R[alpha]-deficient natural killer cells survive in normal but not IL-15R[alpha]-deficient mice. J Exp Med. 2003;197(8):977–84.PubMedCentralPubMedCrossRefGoogle Scholar
  45. 45.
    Prlic M, Blazar BR, Farrar MA, Jameson SC. In vivo survival and homeostatic proliferation of natural killer cells. J Exp Med. 2003;197(8):967–76.PubMedCentralPubMedCrossRefGoogle Scholar
  46. 46.
    Ranson T, Vosshenrich CA, Corcuff E, Richard O, Muller W, Di Santo JP. IL-15 is an essential mediator of peripheral NK-cell homeostasis. Blood. 2003;101(12):4887–93.PubMedCrossRefGoogle Scholar
  47. 47.
    Ranson T, Vosshenrich CA, Corcuff E, Richard O, Laloux V, Lehuen A, et al. IL-15 availability conditions homeostasis of peripheral natural killer T cells. Proc Natl Acad Sci U S A. 2003;100(5):2663–8.PubMedCentralPubMedCrossRefGoogle Scholar
  48. 48.
    Biron CA, Brossay L. NK cells and NKT cells in innate defense against viral infections. Curr Opin Immunol. 2001;13(4):458–64.PubMedCrossRefGoogle Scholar
  49. 49.
    Lanier LL. On guard—activating NK cell receptors. Nat Immunol. 2001;2(1):23–7.PubMedCrossRefGoogle Scholar
  50. 50.
    Lanier LL. Natural killer cell receptor signaling. Curr Opin Immunol. 2003;15(3):308–14.PubMedCrossRefGoogle Scholar
  51. 51.
    Narni-Mancinelli E, Chaix J, Fenis A, Kerdiles YM, Yessaad N, Reynders A, et al. Fate mapping analysis of lymphoid cells expressing the NKp46 cell surface receptor. Proc Natl Acad Sci U S A. 2011;108(45):18324–9. doi: 10.1073/Pnas.1112064108.PubMedCentralPubMedCrossRefGoogle Scholar
  52. 52.
    Raulet D. Roles of the NKG2D immunoreceptor and its ligands. Nat Rev Immunol. 2003;3(10):781–90.PubMedCrossRefGoogle Scholar
  53. 53.
    Vivier E, Anfossi N. Inhibitory NK-cell receptors on T cells: witness of the past, actors of the future. Nat Rev Immunol. 2004;4(3):190–8.PubMedCrossRefGoogle Scholar
  54. 54.
    Yokoyama WM, Plougastel BF. Immune functions encoded by the natural killer gene complex. Nat Rev Immunol. 2003;3(4):304–16.PubMedCrossRefGoogle Scholar
  55. 55.
    Raulet D. Interplay of natural killer cells and their receptors with the adaptive immune response. Nat Immunol. 2004;5(10):996–1002.PubMedCrossRefGoogle Scholar
  56. 56.
    Trinchieri G. Biology of natural killer cells. Adv Immunol. 1989;47:187–376.PubMedCrossRefGoogle Scholar
  57. 57.
    Ferlazzo G, Tsang ML, Moretta L, Melioli G, Steinman R, Munz C. Human dendritic cells activate resting natural killer (NK) cells and are recognized via the NKp30 receptor by activated NK cells. J Exp Med. 2002;195(3):343–51.PubMedCentralPubMedCrossRefGoogle Scholar
  58. 58.
    Gerosa F, Baldani-Guerra B, Nisii C, Marchesini V, Carra G, Trinchieri G. Reciprocal activating interaction between natural killer cells and dendritic cells. J Exp Med. 2002;195(3):327–33.PubMedCentralPubMedCrossRefGoogle Scholar
  59. 59.
    Piccioli D, Sbrana S, Melandri E, Valiante NM. Contact-dependent stimulation and inhibition of dendritic cells by natural killer cells. J Exp Med. 2002;195(3):335–41.PubMedCentralPubMedCrossRefGoogle Scholar
  60. 60.
    Andrews DM, Scalzo AA, Yokoyama WM, Smyth MJ, Degli-Esposti MA. Functional interactions between dendritic cells and NK cells during viral infection. Nat Immunol. 2003;4(2):175–81.PubMedCrossRefGoogle Scholar
  61. 61.
    Moretta A. Natural killer cells and dendritic cells: rendezvous in abused tissues. Nat Rev Immunol. 2002;2(12):957–64.PubMedCrossRefGoogle Scholar
  62. 62.
    Kos FJ. Regulation of adaptive immunity by natural killer cells. Immunol Res. 1998;17(3):303–12.PubMedCrossRefGoogle Scholar
  63. 63.
    Su HC, Nguyen KB, Salazar-Mather TP, Ruzek MC, Dalod MY, Biron CA. NK cell functions restrain T cell responses during viral infections. Eur J Immunol. 2001;31(10):3048–55.PubMedCrossRefGoogle Scholar
  64. 64.
    Diefenbach A, Jensen ER, Jamieson AM, Raulet DH. Rae1 and H60 ligands of the NKG2D receptor stimulate tumour immunity. Nature. 2001;413(6852):165–71.PubMedCentralPubMedCrossRefGoogle Scholar
  65. 65.
    Diefenbach A, Raulet D. The innate immune response to tumors and its role in the induction of T-cell immunity. Immunol Rev. 2002;188:9–21.PubMedCrossRefGoogle Scholar
  66. 66.••
    Karimi K, Forsythe P. Natural killer cells in asthma. Front Immunol. 2013;4:159. doi: 10.3389/Fimmu.2013.00159. This Review Examines The Role Of NK Cells In Asthma And Discusses The Potential Of Modulating NK Cell Function As A Treatment Strategy.
  67. 67.
    Timonen T, Stenius-Aarniala B. Natural killer cell activity in asthma. Clin Exp Immunol. 1985;59(1):85–90.PubMedCentralPubMedGoogle Scholar
  68. 68.
    Jira M, Antosova E, Vondra V, Strejcek J, Mazakova H, Prazakova J. Natural killer and interleukin-2 induced cytotoxicity in asthmatics. I. Effect of acute antigen-specific challenge. Allergy. 1988;43(4):294–8.PubMedCrossRefGoogle Scholar
  69. 69.
    Krejsek J, Kral B, Vokurkova D, Derner V, Touskova M, Parakova Z, et al. Decreased peripheral blood gamma delta T cells in patients with bronchial asthma. Allergy. 1998;53(1):73–7.PubMedCrossRefGoogle Scholar
  70. 70.
    Vesterinen E, Timonen T. Natural killer cell activity in specific and non-specific bronchial challenge. Ann Allergy. 1988;60(3):247–9.PubMedGoogle Scholar
  71. 71.
    Lin SJ, Chang LY, Yan DC, Huang YJ, Lin TJ, Lin TY. Decreased intercellular adhesion molecule-1 (CD54) and L-selectin (CD62L) expression on peripheral blood natural killer cells in asthmatic children with acute exacerbation. Allergy. 2003;58(1):67–71.PubMedCrossRefGoogle Scholar
  72. 72.
    Means-Markwell M, Burgess T, Dekeratry D, O’neil K, Mascola J, Fleisher T, et al. Eosinophilia with aberrant T cells and elevated serum levels of interleukin-2 and interleukin-15. N Engl J Med. 2000;342(21):1568–71.PubMedCrossRefGoogle Scholar
  73. 73.
    Werfel T, Boeker M, Kapp A. Rapid expression of the CD69 antigen on T cells and natural killer cells upon antigenic stimulation of peripheral blood mononuclear cell suspensions. Allergy. 1997;52(4):465–9.PubMedCrossRefGoogle Scholar
  74. 74.
    Kusaka Y, Sato K, Zhang Q, Morita A, Kasahara T, Yanagihara Y. Association of natural killer cell activity with serum IgE. Int Arch Allergy Immunol. 1997;112(4):331–5.PubMedCrossRefGoogle Scholar
  75. 75.
    Sin B, Misirligil Z, Aybay C, Gurbuz L, Imir T. Effect of allergen specific immunotherapy (IT) on natural killer cell activity (NK), IgE, IFN-gamma levels and clinical response in patients with allergic rhinitis and asthma. J Investig Allergol Clin Immunol. 1996;6(6):341–7.PubMedGoogle Scholar
  76. 76.
    Korsgren M. NK cells and asthma. Curr Pharm Des. 2002;8(20):1871–6.PubMedCrossRefGoogle Scholar
  77. 77.
    Lundahl J, Hansson M. Natural killer cells in the airways: do they matter? Allergy. 2003;58(1):2–4.PubMedCrossRefGoogle Scholar
  78. 78.
    Lisbonne M, Diem S, De Castro KA, Lefort J, Araujo LM, Hachem P, et al. Cutting edge: invariant V alpha 14 NKT cells are required for allergen-induced airway inflammation and hyperreactivity in an experimental asthma model. J Immunol. 2003;171(4):1637–41.PubMedCrossRefGoogle Scholar
  79. 79.
    Kim S, Iizuka K, Aguila HL, Weissman IL, Yokoyama WM. In vivo natural killer cell activities revealed by natural killer cell-deficient mice. Proc Natl Acad Sci U S A. 2000;97(6):2731–6.PubMedCentralPubMedCrossRefGoogle Scholar
  80. 80.
    Bogen SA, Fogelman I, Abbas AK. Analysis of IL-2, IL-4, and IFN-gamma-producing cells in situ during immune responses to protein antigens. J Immunol. 1993;150(10):4197–205.PubMedGoogle Scholar
  81. 81.
    Carnaud C, Lee D, Donnars O, Park S, Beavis A, Koezuka Y, et al. Cutting edge: cross-talk between cells of the innate immune system: NKT cells rapidly activate NK cells. J Immunol. 1999;163(9):4647–50.PubMedGoogle Scholar
  82. 82.
    Mehrotra PT, Donnelly RP, Wong S, Kanegane H, Geremew A, Mostowski HS, et al. Production of IL-10 by human natural killer cells stimulated with IL-2 and/or IL-12. J Immunol. 1998;160(6):2637–44.PubMedGoogle Scholar
  83. 83.
    Warren HS, Kinnear BF, Phillips JH, Lanier LL. Production of IL-5 by human NK cells and regulation of IL-5 secretion by IL-4, IL-10, and IL-12. J Immunol. 1995;154(10):5144–52.PubMedGoogle Scholar
  84. 84.
    Hoshino T, Winkler-Pickett RT, Mason AT, Ortaldo JR, Young HA. IL-13 production by NK cells: IL-13-producing NK and T cells are present in vivo in the absence of IFN-gamma. J Immunol. 1999;162(1):51–9.PubMedGoogle Scholar
  85. 85.
    Hoshino T, Wiltrout RH, Young HA. IL-18 is a potent coinducer of IL-13 in NK and T cells: a new potential role for IL-18 in modulating the immune response. J Immunol. 1999;162(9):5070–7.PubMedGoogle Scholar
  86. 86.
    Walker C, Checkel J, Cammisuli S, Leibson PJ, Gleich GJ. IL-5 production by NK cells contributes to eosinophil infiltration in a mouse model of allergic inflammation. J Immunol. 1998;161(4):1962–9.PubMedGoogle Scholar
  87. 87.
    Peritt D, Robertson S, Gri G, Showe L, Aste-Amezaga M, Trinchieri G. Differentiation of human NK cells into NK1 and NK2 subsets. J Immunol. 1998;161(11):5821–4.PubMedGoogle Scholar
  88. 88.
    Deniz G, Akdis M, Aktas E, Blaser K, Akdis CA. Human NK1 and NK2 subsets determined by purification of IFN-gamma-secreting and IFN-gamma-nonsecreting NK cells. Eur J Immunol. 2002;32(3):879–84.PubMedCrossRefGoogle Scholar
  89. 89.
    Wei H, Zhang J, Xiao W, Feng J, Sun R, Tian Z. Involvement of human natural killer cells in asthma pathogenesis: natural killer 2 cells in type 2 cytokine predominance. J Allergy Clin Immunol. 2005;115(4):841–7. doi: 10.1016/J.Jaci.2004.11.026.PubMedCrossRefGoogle Scholar
  90. 90.
    Wingett D, Nielson CP. Divergence in NK cell and cyclic amp regulation of T cell CD40L expression in asthmatic subjects. J Leukoc Biol. 2003;74(4):531–41. doi: 10.1189/Jlb.0303103.PubMedCrossRefGoogle Scholar
  91. 91.
    Kaiko GE, Phipps S, Angkasekwinai P, Dong C, Foster PS. NK cell deficiency predisposes to viral-induced Th2-type allergic inflammation via epithelial-derived IL-25. J Immunol. 2010;185(8):4681–90. doi: 10.4049/Jimmunol.1001758.PubMedCrossRefGoogle Scholar
  92. 92.
    Scordamaglia F, Balsamo M, Scordamaglia A, Moretta A, Mingari MC, Canonica GW, et al. Perturbations of natural killer cell regulatory functions in respiratory allergic diseases. J Allergy Clin Immunol. 2008;121(2):479–85. doi: 10.1016/J.Jaci.2007.09.047.PubMedCrossRefGoogle Scholar
  93. 93.
    Arase N, Arase H, Hirano S, Yokosuka T, Sakurai D, Saito T. IgE-mediated activation of NK cells through Fc gamma RIII. J Immunol. 2003;170(6):3054–8.PubMedCrossRefGoogle Scholar
  94. 94.
    Vosskuhl K, Greten TF, Manns MP, Korangy F, Wedemeyer J. Lipopolysaccharide-mediated mast cell activation induces IFN-gamma secretion by NK cells. J Immunol. 2010;185(1):119–25. doi: 10.4049/Jimmunol.0902406.PubMedCrossRefGoogle Scholar
  95. 95.
    Ferlazzo G, Morandi B. Cross-talks between natural killer cells and distinct subsets of dendritic cells. Front Immunol. 2014;5:159. doi: 10.3389/Fimmu.2014.00159.PubMedCentralPubMedCrossRefGoogle Scholar
  96. 96.••
    Haworth O, Cernadas M, Levy BD. NK cells are effectors for resolvin E1 in the timely resolution of allergic airway inflammation. J Immunol. 2011;186(11):6129–35. doi: 10.4049/Jimmunol.1004007. This Article Demonstrates A Role For NK Cells In The Clearance Of Eosinophil And Antigen-Specific T Cells After The Cessation Of Allergic Responses. NK Cells In The Model Express The Receptor For Resolvin E1, Which Regulated NK Cell Migration And Cytotoxicity During The Resolution Of The Response.

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  1. 1.Department of Pharmaceutical and Administrative Sciences, College of PharmacyWestern New England UniversitySpringfieldUSA

Personalised recommendations