Apoptotic cells induce Mer tyrosine kinase-dependent blockade of NF-kappaB activation in dendritic cells.
Blood
; 109(2): 653-60, 2007 Jan 15.
Article
em En
| MEDLINE
| ID: mdl-17008547
ABSTRACT
Dendritic cells (DCs) play a key role in immune homeostasis and maintenance of self-tolerance. Tolerogenic DCs can be established by an encounter with apoptotic cells (ACs) and subsequent inhibition of maturation and effector functions. The receptor(s) and signaling pathway(s) involved in AC-induced inhibition of DCs have yet to be defined. We demonstrate that pretreatment with apoptotic but not necrotic cells inhibits activation of IkappaB kinase (IKK) and downstream NF-kappaB. Notably, receptor tyrosine kinase Mer (MerTK) binding of ACs is required for mediating this effect. Monocyte-derived DCs lacking MerTK expression (MerTKKD) or treated with blocking MerTK-specific antibodies (Abs) are resistant to AC-induced inhibition and continue to activate NF-kappaB and secrete proinflammatory cytokines. Blocking MerTK activation of the phosphatidylinositol 3-kinase (PI3K)/AKT pathway prevents AC-induced inhibition. These results demonstrate an essential role for MerTK-mediated regulation of the PI3K/AKT and NF-kappaB pathways in AC-induced inhibition of monocyte-derived DCs.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Células Dendríticas
/
NF-kappa B
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Proteínas Proto-Oncogênicas
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Apoptose
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Receptores Proteína Tirosina Quinases
Limite:
Animals
Idioma:
En
Revista:
Blood
Ano de publicação:
2007
Tipo de documento:
Article
País de afiliação:
Estados Unidos