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

TitleDendritic-cell maturation alters intracellular signaling networks, enabling differential effects of IFN-alpha/beta on antigen cross-presentation.
Publication TypeJournal Article
Year of Publication2007
AuthorsLongman RS, Braun D, Pellegrini S, Rice CM, Darnell RB, Albert ML
JournalBlood
Volume109
Issue3
Pagination1113-22
Date Published2007 Feb 1
ISSN0006-4971
KeywordsAnimals, Antigen Presentation, CD8-Positive T-Lymphocytes, Dendritic Cells, Gene Expression Profiling, Gene Expression Regulation, Interferon-alpha, Interferon-beta, Lymphocyte Activation, Mice, Receptor, Interferon alpha-beta, Signal Transduction, STAT1 Transcription Factor, STAT4 Transcription Factor
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.

DOI10.1182/blood-2006-05-023465
Alternate JournalBlood
PubMed ID17018853
Grant ListGM07739 / GM / NIGMS NIH HHS / United States
M01-RR00102 / RR / NCRR NIH HHS / United States
R01 CA85784 / CA / NCI NIH HHS / United States