Osteopontin expression is essential for interferon-alpha production by plasmacytoid dendritic cells.
Nat Immunol
; 7(5): 498-506, 2006 May.
Article
em En
| MEDLINE
| ID: mdl-16604075
ABSTRACT
The observation that the T-bet transcription factor allows tissue-specific upregulation of intracellular osteopontin (Opn-i) in plasmacytoid dendritic cells (pDCs) suggests that Opn might contribute to the expression of interferon-alpha (IFN-alpha) in those cells. Here we show that Opn deficiency substantially reduced Toll-like receptor 9 (TLR9)-dependent IFN-alpha responses but spared expression of transcription factor NF-kappaB-dependent proinflammatory cytokines. Shortly after TLR9 engagement, colocalization of Opn-i and the adaptor molecule MyD88 was associated with induction of transcription factor IRF7-dependent IFN-alpha gene expression, whereas deficient expression of Opn-i was associated with defective nuclear translocation of IRF7 in pDCs. The importance of the Opn-IFN-alpha pathway was emphasized by its essential involvement in cross-presentation in vitro and in anti-herpes simplex virus 1 IFN-alpha response in vivo. The finding that Opn-i selectively coupled TLR9 signaling to expression of IFN-alpha but not to that of other proinflammatory cytokines provides new molecular insight into the biology of pDCs.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Sialoglicoproteínas
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Células Dendríticas
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Interferon-alfa
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Células Mieloides
Limite:
Animals
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Humans
Idioma:
En
Ano de publicação:
2006
Tipo de documento:
Article