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HIF-1α- and hypoxia-dependent immune responses in human CD4+CD25high T cells and T helper 17 cells.

  • Bollinger T Department of Molecular Biology, University of Geneva, Switzerland; Institute of Medical Microbiology and Hygiene, University of Lübeck, Germany; thomas.bollinger@unige.ch.
  • Gies S Institute of Medical Microbiology and Hygiene, University of Lübeck, Germany;
  • Naujoks J Institute of Medical Microbiology and Hygiene, University of Lübeck, Germany;
  • Feldhoff L Institute of Medical Microbiology and Hygiene, University of Lübeck, Germany;
  • Bollinger A Division of Immunology and Allergy, Department of Medical Specialties, University Hospital and Medical Faculty, Geneva, Switzerland; and.
  • Solbach W Institute of Medical Microbiology and Hygiene, University of Lübeck, Germany;
  • Rupp J Institute of Medical Microbiology and Hygiene, University of Lübeck, Germany; Medical Clinic III/Infectious Diseases, University Hospital Schleswig-Holstein/Campus Lübeck, Germany.
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  • 2014-03-26
Published in:
  • Journal of leukocyte biology. - 2014
DMOG
Th17
Treg
YC-1
cytokines
Animals
CD4 Antigens
Cytokines
Enzyme Activators
Female
Humans
Hypoxia-Inducible Factor 1, alpha Subunit
Indazoles
Interleukin-2 Receptor alpha Subunit
Male
Mice
T-Lymphocytes, Regulatory
Th17 Cells
English The central oxygen sensitive transcription factor HIF-1α has been implicated in the differentiation of n(T(reg)) and Th17 cells and to orchestrate metabolic changes of activated T cells. However, data on the functional relevance of HIF-1α and Hox, in general, for nT(reg)-suppressive activity and T cell function in primary human cells are still missing. Therefore, we analyzed the effect of Hox and HIF-1α on human T(res), n(Treg), and Th17 cells. Under Hox, nT(reg)-mediated suppression of T(res) proliferation, CD25 expression, and secretion of IFN-γ were significantly reduced, whereas expression levels of VEGF, TNF-α, and IL-10 were significantly increased. In contrast to observations in mice, Th17 lineage commitment, as determined by RORγt expression, was not affected by activation or inhibition of HIF-1α expression using DMOG or YC-1 treatment, respectively. Nevertheless, the secretion of IL-17A was increased by DMOG and reduced by YC-1 under Th17-skewing conditions in a dose- dependent manner. In conclusion, Hox and HIF-1α substantially influence human T cell-mediated immune responses by modulation of nT(reg)-suppressive function and IL-17A secretion by Th17 cells.
Language
  • English
Open access status
bronze
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Persistent URL
https://folia.unifr.ch/global/documents/62323
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