Transcription regulates HIF-1α expression in CD4(+) T cells
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Transcription regulates HIF-1α expression in CD4(+) T cells. / Bollinger, Thomas; Bollinger, Annalena; Gies, Sydney; Feldhoff, Lea; Solbach, Werner; Rupp, Jan.
In: IMMUNOL CELL BIOL, Vol. 94, No. 1, 01.2016, p. 109-13.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Transcription regulates HIF-1α expression in CD4(+) T cells
AU - Bollinger, Thomas
AU - Bollinger, Annalena
AU - Gies, Sydney
AU - Feldhoff, Lea
AU - Solbach, Werner
AU - Rupp, Jan
PY - 2016/1
Y1 - 2016/1
N2 - 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 (O2⩽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.
AB - 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 (O2⩽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.
KW - CD4-Positive T-Lymphocytes/immunology
KW - Female
KW - Gene Expression Regulation
KW - Humans
KW - Hypoxia-Inducible Factor 1, alpha Subunit/genetics
KW - Lymphocyte Activation/immunology
KW - Male
KW - Protein Stability
KW - RNA, Messenger/genetics
KW - Transcription, Genetic
U2 - 10.1038/icb.2015.64
DO - 10.1038/icb.2015.64
M3 - SCORING: Journal article
C2 - 26150319
VL - 94
SP - 109
EP - 113
JO - IMMUNOL CELL BIOL
JF - IMMUNOL CELL BIOL
SN - 0818-9641
IS - 1
ER -