Beschreibung:
<jats:p>Plasmacytoid dendritic cells (p<jats:styled-content style="fixed-case">DC</jats:styled-content>s) are key players in antiviral immunity. In addition to massive type <jats:styled-content style="fixed-case">I</jats:styled-content> interferon production, activated p<jats:styled-content style="fixed-case">DC</jats:styled-content>s express the apoptosis‐inducing molecule <jats:styled-content style="fixed-case">TRAIL</jats:styled-content>, which enables them to clear infected cells that express the <jats:styled-content style="fixed-case">TRAIL</jats:styled-content> receptors <jats:styled-content style="fixed-case">TRAIL‐R</jats:styled-content>1 and <jats:styled-content style="fixed-case">TRAIL‐R</jats:styled-content>2. In this study, we examined the molecular mechanisms that govern <jats:styled-content style="fixed-case">TRAIL</jats:styled-content> expression in human p<jats:styled-content style="fixed-case">DC</jats:styled-content>s. We identify <jats:styled-content style="fixed-case">NGFI‐A</jats:styled-content>‐binding protein 2 (<jats:styled-content style="fixed-case">NAB</jats:styled-content>2) as a novel transcriptional regulator that governs <jats:styled-content style="fixed-case">TRAIL</jats:styled-content> induction in stimulated p<jats:styled-content style="fixed-case">DC</jats:styled-content>s. We show with the p<jats:styled-content style="fixed-case">DC</jats:styled-content>‐like cell line <jats:styled-content style="fixed-case">CAL</jats:styled-content>‐1 that <jats:styled-content style="fixed-case">NAB</jats:styled-content>2 is exclusively induced downstream of <jats:styled-content style="fixed-case">TLR</jats:styled-content>7 and <jats:styled-content style="fixed-case">TLR</jats:styled-content>9 signaling, and not upon type <jats:styled-content style="fixed-case">I IFN‐R</jats:styled-content> signaling. Furthermore, <jats:styled-content style="fixed-case">PI</jats:styled-content>3<jats:styled-content style="fixed-case">K</jats:styled-content> signaling is required for <jats:styled-content style="fixed-case">NAB</jats:styled-content>2‐mediated <jats:styled-content style="fixed-case">TRAIL</jats:styled-content> expression. Finally, we show that <jats:styled-content style="fixed-case">TRAIL</jats:styled-content> induction in <jats:styled-content style="fixed-case">C</jats:styled-content>p<jats:styled-content style="fixed-case">G</jats:styled-content>‐activated human p<jats:styled-content style="fixed-case">DC</jats:styled-content>s occurs through two independent signaling pathways: the first is initiated through <jats:styled-content style="fixed-case">TLR</jats:styled-content>9 signaling upon recognition of nucleic acids, followed by type <jats:styled-content style="fixed-case">I IFN‐R</jats:styled-content>‐mediated signaling. In conclusion, our data suggest that these two pathways are downstream of different activation signals, but act in concert to allow for full <jats:styled-content style="fixed-case">TRAIL</jats:styled-content> expression in p<jats:styled-content style="fixed-case">DC</jats:styled-content>s.</jats:p>