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Biological Chemistry

Editor-in-Chief: Brüne, Bernhard

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

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Volume 394, Issue 4 (Apr 2013)


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

Regina Wobben
  • Institut für Physiologie, Universität Duisburg-Essen, D-45122 Essen, Germany
/ Yvonne Hüsecken
  • Institut für Physiologie, Universität Duisburg-Essen, D-45122 Essen, Germany
/ Claudia Lodewick
  • Institut für Physiologie, Universität Duisburg-Essen, D-45122 Essen, Germany
/ Kathrin Gibbert
  • Institut für Virologie, Universität Duisburg-Essen, D-45122 Essen, Germany
/ Joachim Fandrey
  • Corresponding author
  • Institut für Physiologie, Universität Duisburg-Essen, D-45122 Essen, Germany
  • Email:
/ Sandra Winning
  • Institut für Physiologie, Universität Duisburg-Essen, D-45122 Essen, Germany
Published Online: 2013-02-28 | DOI: https://doi.org/10.1515/hsz-2012-0320


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

About the article

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

Received: 2012-11-06

Accepted: 2013-01-21

Published Online: 2013-02-28

Published in Print: 2013-04-01

Citation Information: Biological Chemistry, ISSN (Online) 1437-4315, ISSN (Print) 1431-6730, DOI: https://doi.org/10.1515/hsz-2012-0320. Export Citation

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