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- Title
Osteopontin expression is essential for interferon-α production by plasmacytoid dendritic cells.
- Authors
Shinohara, Mari L.; Lu, Linrong; Bu, Jing; Werneck, Miriam B. F.; Kobayashi, Koichi S.; Glimcher, Laurie H.; Cantor, Harvey
- 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-α (IFN-α) in those cells. Here we show that Opn deficiency substantially reduced Toll-like receptor 9 (TLR9)–dependent IFN-α responses but spared expression of transcription factor NF-κB–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-α gene expression, whereas deficient expression of Opn-i was associated with defective nuclear translocation of IRF7 in pDCs. The importance of the Opn–IFN-α pathway was emphasized by its essential involvement in cross-presentation in vitro and in anti–herpes simplex virus 1 IFN-α response in vivo. The finding that Opn-i selectively coupled TLR9 signaling to expression of IFN-α but not to that of other proinflammatory cytokines provides new molecular insight into the biology of pDCs.
- Subjects
TRANSCRIPTION factors; OSTEOPONTIN; CELL adhesion molecules; CYTOKINES; CELLULAR immunity; IMMUNOREGULATION
- Publication
Nature Immunology, 2006, Vol 7, Issue 5, p498
- ISSN
1529-2908
- Publication type
Article
- DOI
10.1038/ni1327