Nature Immunology 7, 498 - 506 (2006)
Published online: 9 April 2006; | doi:10.1038/ni1327
Osteopontin expression is essential for interferon- production by plasmacytoid dendritic cellsMari L Shinohara1, 2, Linrong Lu1, 2, Jing Bu1, 2, Miriam B F Werneck1, 2, Koichi S Kobayashi1, 2, Laurie H Glimcher3, 4
& Harvey Cantor1, 21
Department of Cancer Immunology & AIDS, Dana-Farber Cancer Institute, Harvard School of Public Health, Boston, Massachusetts 02115, USA. 2
Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115, USA. 3
Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, Massachusetts 02115, USA. 4
Department of Medicine, Harvard Medical School, Boston, Massachusetts 02115, USA.
Correspondence should be addressed to Harvey Cantor harvey_cantor@dfci.harvard.edu 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- (IFN-) in those cells. Here we show that Opn deficiency substantially reduced Toll-like receptor 9 (TLR9)–dependent IFN- responses but spared expression of transcription factor NF- B–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- gene expression, whereas deficient expression of Opn-i was associated with defective nuclear translocation of IRF7 in pDCs. The importance of the Opn–IFN- pathway was emphasized by its essential involvement in cross-presentation in vitro and in anti–herpes simplex virus 1 IFN- response in vivo. The finding that Opn-i selectively coupled TLR9 signaling to expression of IFN- but not to that of other proinflammatory cytokines provides new molecular insight into the biology of pDCs.
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