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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
 
 

Osteopontin expression is essential for interferon-alpha production by plasmacytoid dendritic cells.

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.[1]

References

  1. Osteopontin expression is essential for interferon-alpha production by plasmacytoid dendritic cells. Shinohara, M.L., Lu, L., Bu, J., Werneck, M.B., Kobayashi, K.S., Glimcher, L.H., Cantor, H. Nat. Immunol. (2006) [Pubmed]
 
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