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Abstract
The central oxygen sensitive transcription factor HIF-1α has been implicated in the differentiation of nTreg 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 nTreg-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 Tres, nTreg, and Th17 cells. Under Hox, nTreg-mediated suppression of Tres 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 nTreg-suppressive function and IL-17A secretion by Th17 cells.
Original language | German |
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Journal | Journal of Leukocyte Biology |
Volume | 96 |
Issue number | August |
Pages (from-to) | 1-8 |
Number of pages | 8 |
ISSN | 0741-5400 |
DOIs | |
Publication status | Published - 2014 |
Research Areas and Centers
- Academic Focus: Center for Infection and Inflammation Research (ZIEL)
DFG Research Classification Scheme
- 2.21-05 Immunology
Projects
- 1 Active
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DFG Major Research Instrumentation: High-End Cell Sorter (CAnaCore)
01.01.12 → …
Project: DFG Projects › DFG Major Research Instrumentation