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Biological Chemistry

Editor-in-Chief: Brüne, Bernhard

Editorial Board Member: Buchner, Johannes / Ludwig, Stephan / Sies, Helmut / Turk, Boris / Wittinghofer, Alfred

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Role of hypoxia inducible factor-1α for interferon synthesis in mouse dendritic cells

Regina Wobben1 / Yvonne Hüsecken1 / Claudia Lodewick1 / Kathrin Gibbert2 / 1 / Sandra Winning1

1Institut für Physiologie, Universität Duisburg-Essen, D-45122 Essen, Germany

2Institut für Virologie, Universität Duisburg-Essen, D-45122 Essen, Germany

Corresponding author: Joachim Fandrey, Institut für Physiologie, Universität Duisburg-Essen, D-45122 Essen, Germany

Citation Information: Biological Chemistry. Volume 394, Issue 4, Pages 495–505, ISSN (Online) 1437-4315, ISSN (Print) 1431-6730, DOI: 10.1515/hsz-2012-0320, February 2013

Publication History

Received:
2012-11-06
Accepted:
2013-01-21
Published Online:
2013-02-28

Abstract

Dendritic cells (DCs) are an important link between innate and adaptive immunity. DCs get activated in inflamed tissues where oxygen tension is usually low, which requires the transcription factor hypoxia inducible factor (HIF)-1 for cellular adaptation. To investigate whether the HIF-1 transcriptional complex plays a pivotal role in the function of DCs, we compared the effects of exogenous inflammatory stimuli and hypoxia on HIF-1α in bone marrow-derived DCs from wild type and myeloid-specific HIF-1α knock-out mice. We showed that the Toll-like receptor ligands lipopolysaccharides and cytosine-phosphatidyl-guanines significantly induce HIF-1α mRNA and protein, leading to elevated HIF-1 target gene expression of vascular endothelial growth factor. In contrast, polyinosinic:polycytidylic acid did not show comparable effects. Furthermore the potential to up-regulate inflammatory cytokines critically influences DC function. Our data demonstrate that HIF-1α protein is needed for adequate production of interferon-α and -β. In co-cultures of DCs and cytotoxic T cells, we observed that DCs lacking active HIF-1α protein induce significantly less CD278 and granzyme B mRNA in T cells. We conclude that HIF-1α plays a crucial role in DC interferon production and T cell activation, linking the innate and adaptive immune system.

Keywords: dendritic cells; hypoxia; inflammation; type I interferons

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