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

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Shinohara, ML; Lu, L; Bu, J; Werneck, MBF; Kobayashi, KS; Glimcher, LH; Cantor, H

Published Date

  • May 2006

Published In

Volume / Issue

  • 7 / 5

Start / End Page

  • 498 - 506

PubMed ID

  • 16604075

International Standard Serial Number (ISSN)

  • 1529-2908

Digital Object Identifier (DOI)

  • 10.1038/ni1327

Language

  • eng

Conference Location

  • United States