HIF-1α- and hypoxia-dependent immune responses in human CD4+CD25high T cells and T helper 17 cells
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HIF-1α- and hypoxia-dependent immune responses in human CD4+CD25high T cells and T helper 17 cells. / Bollinger, Thomas; Gies, Sydney; Naujoks, Julius; Feldhoff, Lea; Bollinger, Annalena; Solbach, Werner; Rupp, Jan.
in: J LEUKOCYTE BIOL, Jahrgang 96, Nr. 2, 08.2014, S. 305-12.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - HIF-1α- and hypoxia-dependent immune responses in human CD4+CD25high T cells and T helper 17 cells
AU - Bollinger, Thomas
AU - Gies, Sydney
AU - Naujoks, Julius
AU - Feldhoff, Lea
AU - Bollinger, Annalena
AU - Solbach, Werner
AU - Rupp, Jan
N1 - © 2014 Society for Leukocyte Biology.
PY - 2014/8
Y1 - 2014/8
N2 - 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.
AB - 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.
KW - Animals
KW - CD4 Antigens/immunology
KW - Cytokines/immunology
KW - Enzyme Activators/pharmacology
KW - Female
KW - Humans
KW - Hypoxia-Inducible Factor 1, alpha Subunit/immunology
KW - Indazoles/pharmacology
KW - Interleukin-2 Receptor alpha Subunit/immunology
KW - Male
KW - Mice
KW - T-Lymphocytes, Regulatory/cytology
KW - Th17 Cells/cytology
U2 - 10.1189/jlb.3A0813-426RR
DO - 10.1189/jlb.3A0813-426RR
M3 - SCORING: Journal article
C2 - 24664971
VL - 96
SP - 305
EP - 312
JO - J LEUKOCYTE BIOL
JF - J LEUKOCYTE BIOL
SN - 0741-5400
IS - 2
ER -
