ADAM10 and Notch1 on murine dendritic cells control the development of type 2 immunity and IgE production.
Allergy
; 73(1): 125-136, 2018 Jan.
Article
em En
| MEDLINE
| ID: mdl-28745029
ABSTRACT
BACKGROUND:
Allergy and allergic asthma are significant health burdens in developed countries and are increasing in prevalence. Dendritic cells (DCs) initiate immune responses to common aeroallergens, and ADAM10 has been demonstrated to be important for the development of adaptive responses. This study's objective was to understand the role of ADAM10 on DCs in the development of allergic and anaphylactic responses.METHODS:
In this study, we used mouse models of allergic airway inflammation (house dust mice and Alternaria alternata) and OVA-induced models of active anaphylaxis to determine the DC-specific function of ADAM10 and Notch signaling. To examine TH 1 and TH 17 immunity infection with Anaplasma phagocytophilum and Citrobacter rodentium respectively, were used.RESULTS:
Mice, which have ADAM10 deleted from DCs, have dramatic reductions in IgE production and do not develop significant TH 2 immune responses. Further, ADAM10DC-/- mice are resistant to IgE-mediated anaphylaxis. This response is selective for TH 2 immunity as TH 1 and TH 17 immunity is largely unaffected. Notch1, a known ADAM10 substrate, when knocked out of DCs (Notch1DC-/- ) demonstrated a similar reduction in anaphylaxis and IgE. Without ADAM10 and Notch1 signaling, DCs were unable to make cytokines that stimulate TH 2 cells and cytokines. Anaphylaxis and allergic lung inflammation were restored in ADAM10DC-/- with the overexpression of the Notch1-intracellular domain, confirming the role of Notch signaling.CONCLUSIONS:
Targeting ADAM10 and Notch1 on DCs represent a novel strategy for modulating TH 2 immune responses and IgE production.Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Células Dendríticas
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Imunoglobulina E
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Receptor Notch1
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Secretases da Proteína Precursora do Amiloide
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Proteína ADAM10
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Proteínas de Membrana
Tipo de estudo:
Prognostic_studies
/
Risk_factors_studies
Limite:
Animals
Idioma:
En
Revista:
Allergy
Ano de publicação:
2018
Tipo de documento:
Article
País de afiliação:
Estados Unidos