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Transcription regulates HIF‐1α expression in CD4 + T cells
Author(s) -
Bollinger Thomas,
Bollinger Annalena,
Gies Sydney,
Feldhoff Lea,
Solbach Werner,
Rupp Jan
Publication year - 2016
Publication title -
immunology and cell biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.999
H-Index - 104
eISSN - 1440-1711
pISSN - 0818-9641
DOI - 10.1038/icb.2015.64
Subject(s) - nfat , downregulation and upregulation , ionomycin , transcription factor , microbiology and biotechnology , cd28 , t cell , chemistry , biology , cd3 , immune system , immunology , biochemistry , cd8 , gene , intracellular
The transcription factor hypoxia inducible factor‐1α (HIF‐1α) mediates the metabolic adaptation of cells to hypoxia and T‐helper cell fate. However, HIF‐1α regulation in CD4 + T cells (T cells) remains elusive. Here we observed that depletion of oxygen (O 2 ⩽2%) alone was not sufficient to induce HIF‐1α expression in T cells. However, when hypoxic T cells were stimulated, HIF‐1α was expressed and this was dependent on nuclear factor‐κB‐ and nuclear factor of activated T cell (NFAT)‐mediated transcriptional upregulation of Hif‐1α mRNA. HIF‐1α upregulation could be blocked by drugs inhibiting NF‐κB, NFAT or mammalian target of rapamycin precluding CD4 + T‐cell stimulation or translation in T cells, as well as by blocking transcription. CD3, CD28, phorbol‐12‐myristat‐13‐acetat (PMA) or ionomycin‐stimulated T cells did not express HIF‐1α under normoxic conditions. In conclusion, regulation of HIF‐1α expression in CD4 + T cells in hypoxia gravely relies on its transcriptional upregulation and subsequent enhanced protein stabilization.