title: Natural killer cell NKG2D and granzyme B are critical for allergic pulmonary inflammation.
abstract: BACKGROUND
  The diverse roles of innate immune cells in the pathogenesis of asthma remain to be fully defined. Natural killer (NK) cells are innate lymphocytes that can regulate adaptive immune responses. NK cells are activated in asthma; however, their role in allergic airway inflammation is not fully understood.
  
  
  OBJECTIVE
  We investigated the importance of NK cells in house dust mite (HDM)-triggered allergic pulmonary inflammation. Specifically, we aimed to determine the role of the major NK-cell activating receptor NKG2D and NK-cell effector functions mediated by granzyme B.
  
  
  METHODS
  Allergic airway inflammation was induced in the airways of mice by repeated intranasal HDM extract administration and responses in wild-type and NKG2D-deficient mice were compared. Adoptive transfer studies were used to identify the cells and mechanisms involved.
  
  
  RESULTS
  Mice that lacked NKG2D were resistant to the induction of allergic inflammation and showed little pulmonary eosinophilia, few airway TH2 cells, and no rise in serum IgE after multiple HDM-allergen exposures. However, NKG2D was not required for pulmonary inflammation after a single inoculation of allergen. NKG2D-deficient mice showed no alteration in responses to respiratory virus infection. Transfer of wild-type NK cells (but not CD3(+) cells) into NKG2D-deficient mice restored allergic inflammatory responses only if the NK cells expressed granzyme B.
  
  
  CONCLUSIONS
  These studies established a pivotal role for NK-cell NKG2D and granzyme B in the pathogenesis of HDM-induced allergic lung disease, and identified novel therapeutic targets for the prevention and treatment of asthma.
authors.affiliation: Centre for Respiratory Infection and MRC-Asthma UK Centre for Allergic Mechanisms in Asthma, Department of Respiratory Infections, National Heart and Lung Institute, Faculty of Medicine, Imperial College London, London, United Kingdom.
authors.forename: Nazanin
authors.initials: N
authors.lastname: Farhadi
authors.affiliation: Centre for Respiratory Infection and MRC-Asthma UK Centre for Allergic Mechanisms in Asthma, Department of Respiratory Infections, National Heart and Lung Institute, Faculty of Medicine, Imperial College London, London, United Kingdom.
authors.forename: Laura
authors.initials: L
authors.lastname: Lambert
authors.affiliation: Division of Cell and Molecular Biology, Faculty of Natural Sciences, Imperial College London, London, United Kingdom.
authors.forename: Chiara
authors.initials: C
authors.lastname: Triulzi
authors.affiliation: Centre for Respiratory Infection and MRC-Asthma UK Centre for Allergic Mechanisms in Asthma, Department of Respiratory Infections, National Heart and Lung Institute, Faculty of Medicine, Imperial College London, London, United Kingdom.
authors.forename: Peter J M
authors.initials: PJ
authors.lastname: Openshaw
authors.affiliation: Division of Cell and Molecular Biology, Faculty of Natural Sciences, Imperial College London, London, United Kingdom.
authors.forename: Nadia
authors.initials: N
authors.lastname: Guerra
authors.affiliation: Centre for Respiratory Infection and MRC-Asthma UK Centre for Allergic Mechanisms in Asthma, Department of Respiratory Infections, National Heart and Lung Institute, Faculty of Medicine, Imperial College London, London, United Kingdom. Electronic address: f.culley@imperial.ac.uk.
authors.forename: Fiona J
authors.initials: FJ
authors.lastname: Culley
mesh_terms: D000818:Animals; D001249:Asthma / Q000209:etiology* / Q000276:immunology; D005260:Female; D053804:Granzymes / Q000502:physiology*; D007694:Killer Cells, Natural / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D055655:NK Cell Lectin-Like Receptor Subfamily K / Q000502:physiology*; D011014:Pneumonia / Q000209:etiology* / Q000276:immunology; D039981:Pyroglyphidae / Q000276:immunology
chemical_list: C527086:Klrk1 protein, mouse; D055655:NK Cell Lectin-Like Receptor Subfamily K; D053804:Granzymes
keywords: Innate immunity; allergic inflammation; asthma; house dust mite; lung; natural killer cell