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

• Published in: Nature immunology Vol. 7; no. 5; p. 498
• Main Authors: Shinohara, Mari L, Lu, Linrong, Bu, Jing, Werneck, Miriam B F, Kobayashi, Koichi S, Glimcher, Laurie H, Cantor, Harvey
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group 01-05-2006
• Subjects: Translocation
• ISSN: 1529-2908; 1529-2916
• DOI: 10.1038/ni1327

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.