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

Overview

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.

publication date

  • October 3, 2006

Research

keywords

  • Antigen Presentation
  • Dendritic Cells
  • Interferon-alpha
  • Interferon-beta
  • Signal Transduction

Identity

Scopus Document Identifier

  • 33846871508

Digital Object Identifier (DOI)

  • 10.1182/blood-2006-05-023465

PubMed ID

  • 17018853

Additional Document Info

volume

  • 109

issue

  • 3