Dendritic-cell maturation alters intracellular signaling networks, enabling differential effects of IFN-α/β on antigen cross-presentation
- 3 October 2006
- journal article
- Published by American Society of Hematology in Blood
- Vol. 109 (3), 1113-1122
- https://doi.org/10.1182/blood-2006-05-023465
Abstract
The broad and often contrasting effects of type I interferons (IFNs) in innate and adaptive immunity are belied by the signaling via a single receptor, IFN-α receptor (IFNAR). Here, we show that IFN-α/β induces opposing effects on the immunologic outcome of antigen cross-presentation depending on dendritic cell (DC) maturation status. Despite equivalent IFNAR expression, immature conventional DCs (cDCs) activate STAT1 in response to IFN-α/β, whereas exposure of mature DCs to IFN-α/β results in signaling via STAT4. Microarray analysis revealed numerous transcriptional changes resulting from the altered signaling. Importantly, STAT1 signaling resulted in significant inhibition of CD40L-induced IL-12 production, accounting for the inhibition of CD8+ T-cell activation. These data provide evidence for a molecular switch in signaling pathways concomitant with DC maturation that offers a novel mechanism by which DCs modulate the integration of signals from the surrounding environment.Keywords
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