A20-deficient mast cells exacerbate inflammatory responses in vivo.
PLoS Biol
; 12(1): e1001762, 2014 Jan.
Article
em En
| MEDLINE
| ID: mdl-24453940
ABSTRACT
Mast cells are implicated in the pathogenesis of inflammatory and autoimmune diseases. However, this notion based on studies in mast cell-deficient mice is controversial. We therefore established an in vivo model for hyperactive mast cells by specifically ablating the NF-κB negative feedback regulator A20. While A20 deficiency did not affect mast cell degranulation, it resulted in amplified pro-inflammatory responses downstream of IgE/FcεRI, TLRs, IL-1R, and IL-33R. As a consequence house dust mite- and IL-33-driven lung inflammation, late phase cutaneous anaphylaxis, and collagen-induced arthritis were aggravated, in contrast to experimental autoimmune encephalomyelitis and immediate anaphylaxis. Our results provide in vivo evidence that hyperactive mast cells can exacerbate inflammatory disorders and define diseases that might benefit from therapeutic intervention with mast cell function.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Artrite Experimental
/
Ubiquitina-Proteína Ligases
/
Peptídeos e Proteínas de Sinalização Intracelular
/
Proteínas de Ligação a DNA
/
Encefalomielite Autoimune Experimental
/
Anafilaxia
/
Mastócitos
Tipo de estudo:
Prognostic_studies
Idioma:
En
Revista:
PLoS Biol
Assunto da revista:
BIOLOGIA
Ano de publicação:
2014
Tipo de documento:
Article
País de afiliação:
Alemanha