Renner 2017 MiP2017: Difference between revisions
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{{Abstract | {{Abstract | ||
|title=[[Image: | |title=[[Image:IMG 7832.JPG|left|90px|Kathrin Renner-Sattler]] D-2-hydroxyglutarate interferes with HIF-1Ξ± stability skewing T-cell metabolism towards oxidative phosphorylation and impairing Th17 polarization. | ||
|info=[[MiP2017]] | |info=[[MiP2017]] | ||
|authors=Renner K, Boettcher M, Berger R, Mentz K, Thomas S, Zugey Cadenas E, Dettmer K, Oefner P, Mackensen A, Kreutz M, Mougiakakos D | |||
|year=2017 | |year=2017 | ||
|event=MiP2017 | |event=MiP2017 | ||
|abstract=[[Image:MITOEAGLE-logo.jpg|left|100px|link=http://www.mitoglobal.org/index.php/MITOEAGLE|COST Action MITOEAGLE]] | |abstract=[[Image:MITOEAGLE-logo.jpg|left|100px|link=http://www.mitoglobal.org/index.php/MITOEAGLE|COST Action MITOEAGLE]] D-2-hydroxyglutarate (D-2HG) is abundantly released by various types of malignant cells such as acute myeloid leukemia (AML) blasts carrying isocitrate dehydrogenase (IDH) gain-of-function mutations. D-2HG acting as an oncometabolite promotes proliferation, anoikis, and differentiation block of hematopoietic cells in an autocrine fashion. As anticipated, IDH mutations and high D-2HG levels are associated with inferior prognosis in AML. An increasing number of studies focus on the permissive environment created by AML blasts to promote immune evasion. However, impact of D-2HG on immune cells remains unexplored. Here, we sought out to investigate the effects of D-2HG on T-cells as key mediators of the anti-AML immunity. D-2HG is efficiently taken up by T-cells, which is in line with the high 2-HG levels that we occasionally measured in AML patient-derived T-cells. During our short-term cultures we did not observe detrimental effects on responsiveness towards activating stimuli. We noticed a D-2HG-triggered HIF-1Ξ± protein destabilization linked to metabolic skewing towards oxidative phosphorylation and reduced T helper 17 (Th17) cell polarization. In line with these findings, IL-17 and RorΞ³(t), the prototypical Th17 cell transcription factor, were found decreased in AML patient-derived T-cells suggesting for the first time that D-2HG might contribute to fine tuning of immune responses. | ||
|editor=[[Kandolf G]] | |editor=[[Kandolf G]] | ||
}} | }} | ||
{{Labeling}} | {{Labeling | ||
|area=Pharmacology;toxicology | |||
|organism=Human | |||
|tissues=Macrophage-derived | |||
}} | |||
== Affiliations == | == Affiliations == | ||
::::Renner K(1), Boettcher M(2), Berger R(3), Mentz K(2), Thomas S(1), Zugey Cadenas E(1), Dettmer K(3), Oefner P(3), Mackensen A(2), Kreutz M(1), Mougiakakos D(2) | |||
::::#Internal Medicine III, Univ Hospital, Regensburg, Germany | |||
::::#Dept Internal Medicine 5, Hematology Oncology, Univ Erlangen-Nuremberg, Germany | |||
::::#Inst Functional Genomics, Univ Regensburg, Germany. - [email protected] |
Revision as of 18:00, 8 November 2017
D-2-hydroxyglutarate interferes with HIF-1Ξ± stability skewing T-cell metabolism towards oxidative phosphorylation and impairing Th17 polarization. |
Link: MiP2017
Renner K, Boettcher M, Berger R, Mentz K, Thomas S, Zugey Cadenas E, Dettmer K, Oefner P, Mackensen A, Kreutz M, Mougiakakos D (2017)
Event: MiP2017
D-2-hydroxyglutarate (D-2HG) is abundantly released by various types of malignant cells such as acute myeloid leukemia (AML) blasts carrying isocitrate dehydrogenase (IDH) gain-of-function mutations. D-2HG acting as an oncometabolite promotes proliferation, anoikis, and differentiation block of hematopoietic cells in an autocrine fashion. As anticipated, IDH mutations and high D-2HG levels are associated with inferior prognosis in AML. An increasing number of studies focus on the permissive environment created by AML blasts to promote immune evasion. However, impact of D-2HG on immune cells remains unexplored. Here, we sought out to investigate the effects of D-2HG on T-cells as key mediators of the anti-AML immunity. D-2HG is efficiently taken up by T-cells, which is in line with the high 2-HG levels that we occasionally measured in AML patient-derived T-cells. During our short-term cultures we did not observe detrimental effects on responsiveness towards activating stimuli. We noticed a D-2HG-triggered HIF-1Ξ± protein destabilization linked to metabolic skewing towards oxidative phosphorylation and reduced T helper 17 (Th17) cell polarization. In line with these findings, IL-17 and RorΞ³(t), the prototypical Th17 cell transcription factor, were found decreased in AML patient-derived T-cells suggesting for the first time that D-2HG might contribute to fine tuning of immune responses.
β’ Bioblast editor: Kandolf G
Labels: MiParea: Pharmacology;toxicology
Organism: Human
Tissue;cell: Macrophage-derived
Affiliations
- Renner K(1), Boettcher M(2), Berger R(3), Mentz K(2), Thomas S(1), Zugey Cadenas E(1), Dettmer K(3), Oefner P(3), Mackensen A(2), Kreutz M(1), Mougiakakos D(2)
- Internal Medicine III, Univ Hospital, Regensburg, Germany
- Dept Internal Medicine 5, Hematology Oncology, Univ Erlangen-Nuremberg, Germany
- Inst Functional Genomics, Univ Regensburg, Germany. - [email protected]