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Natural killer cell NKG2D and granzyme B are critical for allergic pulmonary inflammation.
Farhadi, Nazanin; Lambert, Laura; Triulzi, Chiara; Openshaw, Peter J M; Guerra, Nadia; Culley, Fiona J.
Afiliación
  • Farhadi N; 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.
  • Lambert L; 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.
  • Triulzi C; Division of Cell and Molecular Biology, Faculty of Natural Sciences, Imperial College London, London, United Kingdom.
  • Openshaw PJ; 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.
  • Guerra N; Division of Cell and Molecular Biology, Faculty of Natural Sciences, Imperial College London, London, United Kingdom.
  • Culley FJ; 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.
J Allergy Clin Immunol ; 133(3): 827-35.e3, 2014 Mar.
Article en En | MEDLINE | ID: mdl-24290277
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neumonía / Asma / Células Asesinas Naturales / Granzimas / Subfamilia K de Receptores Similares a Lectina de Células NK Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: J Allergy Clin Immunol Año: 2014 Tipo del documento: Article País de afiliación: Reino Unido Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neumonía / Asma / Células Asesinas Naturales / Granzimas / Subfamilia K de Receptores Similares a Lectina de Células NK Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: J Allergy Clin Immunol Año: 2014 Tipo del documento: Article País de afiliación: Reino Unido Pais de publicación: Estados Unidos