Dendritic-cell maturation alters intracellular signaling networks, enabling differential effects of IFN-α/β on antigen cross-presentation Journal Article
| Authors: | Longman, R. S.; Braun, D.; Pellegrini, S.; Rice, C. M.; Darnell, R. B.; Albert, M. L. |
| Article Title: | Dendritic-cell maturation alters intracellular signaling networks, enabling differential effects of IFN-α/β 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-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. © 2007 by The American Society of Hematology. |
| Keywords: | signal transduction; controlled study; protein expression; human cell; nonhuman; alpha interferon; outcome assessment; protein function; cd8+ t lymphocyte; cd8-positive t-lymphocytes; animal cell; animals; mice; stat1 protein; gene expression profiling; cell maturation; dendritic cell; transcription initiation; cd40 ligand; gene expression regulation; antigen presentation; immunology; lymphocyte activation; dendritic cells; microarray analysis; cytokine production; beta interferon; t lymphocyte activation; interleukin 12; receptor, interferon alpha-beta; interferon-alpha; interferon-beta; cross presentation; stat4 protein; stat4 transcription factor; alpha interferon receptor; stat1 transcription factor |
| Journal Title: | Blood |
| Volume: | 109 |
| Issue: | 3 |
| ISSN: | 0006-4971 |
| Publisher: | American Society of Hematology |
| Date Published: | 2007-02-01 |
| Start Page: | 1113 |
| End Page: | 1122 |
| Language: | English |
| DOI: | 10.1182/blood-2006-05-023465 |
| PUBMED: | 17018853 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 30" - "Export Date: 17 November 2011" - "CODEN: BLOOA" - "Source: Scopus" |
