Natural killer cell NKG2D and granzyme B are critical for allergic pulmonary inflammation.
J Allergy Clin Immunol
; 133(3): 827-35.e3, 2014 Mar.
Article
em En
| MEDLINE
| ID: mdl-24290277
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.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Pneumonia
/
Asma
/
Células Matadoras Naturais
/
Granzimas
/
Subfamília K de Receptores Semelhantes a Lectina de Células NK
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
J Allergy Clin Immunol
Ano de publicação:
2014
Tipo de documento:
Article
País de afiliação:
Reino Unido