Dendritic-cell maturation alters intracellular signaling networks, enabling differential effects of IFN-alpha/beta on antigen cross-presentation. - Institut Pasteur Access content directly
Journal Articles Blood Year : 2007

Dendritic-cell maturation alters intracellular signaling networks, enabling differential effects of IFN-alpha/beta on antigen cross-presentation.

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-alpha receptor (IFNAR). Here, we show that IFN-alpha/beta 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-alpha/beta, whereas exposure of mature DCs to IFN-alpha/beta 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.

Domains

Immunology

Dates and versions

pasteur-00161659 , version 1 (11-07-2007)

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Cite

Randy S. Longman, Deborah Braun, Sandra Pellegrini, Charles M. Rice, R. Darnell, et al.. Dendritic-cell maturation alters intracellular signaling networks, enabling differential effects of IFN-alpha/beta on antigen cross-presentation.. Blood, 2007, 109 (3), pp.1113-22. ⟨10.1182/blood-2006-05-023465⟩. ⟨pasteur-00161659⟩

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