Early TCR Signaling Induces Rapid Aerobic Glycolysis Enabling Distinct Acute T Cell Effector Functions

Summary: To fulfill bioenergetic demands of activation, T cells perform aerobic glycolysis, a process common to highly proliferative cells in which glucose is fermented into lactate rather than oxidized in mitochondria. However, the signaling events that initiate aerobic glycolysis in T cells remain...
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Autor*in:	Ashley V. Menk [verfasserIn] Nicole E. Scharping [verfasserIn] Rebecca S. Moreci [verfasserIn] Xue Zeng [verfasserIn] Cliff Guy [verfasserIn] Sonia Salvatore [verfasserIn] Heekyong Bae [verfasserIn] Jianxin Xie [verfasserIn] Howard A. Young [verfasserIn] Stacy Gelhaus Wendell [verfasserIn] Greg M. Delgoffe [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2018

Schlagwörter:	immunometabolism glycolysis PDHK1 T cell cytokine LDH

Übergeordnetes Werk:	In: Cell Reports - Elsevier, 2015, 22(2018), 6, Seite 1509-1521
Übergeordnetes Werk:	volume:22 ; year:2018 ; number:6 ; pages:1509-1521

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc

DOI / URN:	10.1016/j.celrep.2018.01.040

Katalog-ID:	DOAJ067872670

Internformat


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520			\|a Summary: To fulfill bioenergetic demands of activation, T cells perform aerobic glycolysis, a process common to highly proliferative cells in which glucose is fermented into lactate rather than oxidized in mitochondria. However, the signaling events that initiate aerobic glycolysis in T cells remain unclear. We show T cell activation rapidly induces glycolysis independent of transcription, translation, CD28, and Akt and not involving increased glucose uptake or activity of glycolytic enzymes. Rather, TCR signaling promotes activation of pyruvate dehydrogenase kinase 1 (PDHK1), inhibiting mitochondrial import of pyruvate and facilitating breakdown into lactate. Inhibition of PDHK1 reveals this switch is required acutely for cytokine synthesis but dispensable for cytotoxicity. Functionally, cytokine synthesis is modulated via lactate dehydrogenase, which represses cytokine mRNA translation when aerobic glycolysis is disengaged. Our data provide mechanistic insight to metabolic contribution to effector T cell function and suggest that T cell function may be finely tuned through modulation of glycolytic activity.
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700	0		\|a Stacy Gelhaus Wendell \|e verfasserin \|4 aut
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publishDate	2018
allfields	10.1016/j.celrep.2018.01.040 doi (DE-627)DOAJ067872670 (DE-599)DOAJ9a323dcf2c784882a7635f4587454ea7 DE-627 ger DE-627 rakwb eng QH301-705.5 Ashley V. Menk verfasserin aut Early TCR Signaling Induces Rapid Aerobic Glycolysis Enabling Distinct Acute T Cell Effector Functions 2018 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Summary: To fulfill bioenergetic demands of activation, T cells perform aerobic glycolysis, a process common to highly proliferative cells in which glucose is fermented into lactate rather than oxidized in mitochondria. However, the signaling events that initiate aerobic glycolysis in T cells remain unclear. We show T cell activation rapidly induces glycolysis independent of transcription, translation, CD28, and Akt and not involving increased glucose uptake or activity of glycolytic enzymes. Rather, TCR signaling promotes activation of pyruvate dehydrogenase kinase 1 (PDHK1), inhibiting mitochondrial import of pyruvate and facilitating breakdown into lactate. Inhibition of PDHK1 reveals this switch is required acutely for cytokine synthesis but dispensable for cytotoxicity. Functionally, cytokine synthesis is modulated via lactate dehydrogenase, which represses cytokine mRNA translation when aerobic glycolysis is disengaged. Our data provide mechanistic insight to metabolic contribution to effector T cell function and suggest that T cell function may be finely tuned through modulation of glycolytic activity. immunometabolism glycolysis PDHK1 T cell cytokine LDH Biology (General) Nicole E. Scharping verfasserin aut Rebecca S. Moreci verfasserin aut Xue Zeng verfasserin aut Cliff Guy verfasserin aut Sonia Salvatore verfasserin aut Heekyong Bae verfasserin aut Jianxin Xie verfasserin aut Howard A. Young verfasserin aut Stacy Gelhaus Wendell verfasserin aut Greg M. Delgoffe verfasserin aut In Cell Reports Elsevier, 2015 22(2018), 6, Seite 1509-1521 (DE-627)684964562 (DE-600)2649101-1 22111247 nnns volume:22 year:2018 number:6 pages:1509-1521 https://doi.org/10.1016/j.celrep.2018.01.040 kostenfrei https://doaj.org/article/9a323dcf2c784882a7635f4587454ea7 kostenfrei http://www.sciencedirect.com/science/article/pii/S221112471830072X kostenfrei https://doaj.org/toc/2211-1247 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2110 GBV_ILN_2112 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4700 AR 22 2018 6 1509-1521
spelling	10.1016/j.celrep.2018.01.040 doi (DE-627)DOAJ067872670 (DE-599)DOAJ9a323dcf2c784882a7635f4587454ea7 DE-627 ger DE-627 rakwb eng QH301-705.5 Ashley V. Menk verfasserin aut Early TCR Signaling Induces Rapid Aerobic Glycolysis Enabling Distinct Acute T Cell Effector Functions 2018 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Summary: To fulfill bioenergetic demands of activation, T cells perform aerobic glycolysis, a process common to highly proliferative cells in which glucose is fermented into lactate rather than oxidized in mitochondria. However, the signaling events that initiate aerobic glycolysis in T cells remain unclear. We show T cell activation rapidly induces glycolysis independent of transcription, translation, CD28, and Akt and not involving increased glucose uptake or activity of glycolytic enzymes. Rather, TCR signaling promotes activation of pyruvate dehydrogenase kinase 1 (PDHK1), inhibiting mitochondrial import of pyruvate and facilitating breakdown into lactate. Inhibition of PDHK1 reveals this switch is required acutely for cytokine synthesis but dispensable for cytotoxicity. Functionally, cytokine synthesis is modulated via lactate dehydrogenase, which represses cytokine mRNA translation when aerobic glycolysis is disengaged. Our data provide mechanistic insight to metabolic contribution to effector T cell function and suggest that T cell function may be finely tuned through modulation of glycolytic activity. immunometabolism glycolysis PDHK1 T cell cytokine LDH Biology (General) Nicole E. Scharping verfasserin aut Rebecca S. Moreci verfasserin aut Xue Zeng verfasserin aut Cliff Guy verfasserin aut Sonia Salvatore verfasserin aut Heekyong Bae verfasserin aut Jianxin Xie verfasserin aut Howard A. Young verfasserin aut Stacy Gelhaus Wendell verfasserin aut Greg M. Delgoffe verfasserin aut In Cell Reports Elsevier, 2015 22(2018), 6, Seite 1509-1521 (DE-627)684964562 (DE-600)2649101-1 22111247 nnns volume:22 year:2018 number:6 pages:1509-1521 https://doi.org/10.1016/j.celrep.2018.01.040 kostenfrei https://doaj.org/article/9a323dcf2c784882a7635f4587454ea7 kostenfrei http://www.sciencedirect.com/science/article/pii/S221112471830072X kostenfrei https://doaj.org/toc/2211-1247 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2110 GBV_ILN_2112 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4700 AR 22 2018 6 1509-1521
allfields_unstemmed	10.1016/j.celrep.2018.01.040 doi (DE-627)DOAJ067872670 (DE-599)DOAJ9a323dcf2c784882a7635f4587454ea7 DE-627 ger DE-627 rakwb eng QH301-705.5 Ashley V. Menk verfasserin aut Early TCR Signaling Induces Rapid Aerobic Glycolysis Enabling Distinct Acute T Cell Effector Functions 2018 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Summary: To fulfill bioenergetic demands of activation, T cells perform aerobic glycolysis, a process common to highly proliferative cells in which glucose is fermented into lactate rather than oxidized in mitochondria. However, the signaling events that initiate aerobic glycolysis in T cells remain unclear. We show T cell activation rapidly induces glycolysis independent of transcription, translation, CD28, and Akt and not involving increased glucose uptake or activity of glycolytic enzymes. Rather, TCR signaling promotes activation of pyruvate dehydrogenase kinase 1 (PDHK1), inhibiting mitochondrial import of pyruvate and facilitating breakdown into lactate. Inhibition of PDHK1 reveals this switch is required acutely for cytokine synthesis but dispensable for cytotoxicity. Functionally, cytokine synthesis is modulated via lactate dehydrogenase, which represses cytokine mRNA translation when aerobic glycolysis is disengaged. Our data provide mechanistic insight to metabolic contribution to effector T cell function and suggest that T cell function may be finely tuned through modulation of glycolytic activity. immunometabolism glycolysis PDHK1 T cell cytokine LDH Biology (General) Nicole E. Scharping verfasserin aut Rebecca S. Moreci verfasserin aut Xue Zeng verfasserin aut Cliff Guy verfasserin aut Sonia Salvatore verfasserin aut Heekyong Bae verfasserin aut Jianxin Xie verfasserin aut Howard A. Young verfasserin aut Stacy Gelhaus Wendell verfasserin aut Greg M. Delgoffe verfasserin aut In Cell Reports Elsevier, 2015 22(2018), 6, Seite 1509-1521 (DE-627)684964562 (DE-600)2649101-1 22111247 nnns volume:22 year:2018 number:6 pages:1509-1521 https://doi.org/10.1016/j.celrep.2018.01.040 kostenfrei https://doaj.org/article/9a323dcf2c784882a7635f4587454ea7 kostenfrei http://www.sciencedirect.com/science/article/pii/S221112471830072X kostenfrei https://doaj.org/toc/2211-1247 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2110 GBV_ILN_2112 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4700 AR 22 2018 6 1509-1521
allfieldsGer	10.1016/j.celrep.2018.01.040 doi (DE-627)DOAJ067872670 (DE-599)DOAJ9a323dcf2c784882a7635f4587454ea7 DE-627 ger DE-627 rakwb eng QH301-705.5 Ashley V. Menk verfasserin aut Early TCR Signaling Induces Rapid Aerobic Glycolysis Enabling Distinct Acute T Cell Effector Functions 2018 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Summary: To fulfill bioenergetic demands of activation, T cells perform aerobic glycolysis, a process common to highly proliferative cells in which glucose is fermented into lactate rather than oxidized in mitochondria. However, the signaling events that initiate aerobic glycolysis in T cells remain unclear. We show T cell activation rapidly induces glycolysis independent of transcription, translation, CD28, and Akt and not involving increased glucose uptake or activity of glycolytic enzymes. Rather, TCR signaling promotes activation of pyruvate dehydrogenase kinase 1 (PDHK1), inhibiting mitochondrial import of pyruvate and facilitating breakdown into lactate. Inhibition of PDHK1 reveals this switch is required acutely for cytokine synthesis but dispensable for cytotoxicity. Functionally, cytokine synthesis is modulated via lactate dehydrogenase, which represses cytokine mRNA translation when aerobic glycolysis is disengaged. Our data provide mechanistic insight to metabolic contribution to effector T cell function and suggest that T cell function may be finely tuned through modulation of glycolytic activity. immunometabolism glycolysis PDHK1 T cell cytokine LDH Biology (General) Nicole E. Scharping verfasserin aut Rebecca S. Moreci verfasserin aut Xue Zeng verfasserin aut Cliff Guy verfasserin aut Sonia Salvatore verfasserin aut Heekyong Bae verfasserin aut Jianxin Xie verfasserin aut Howard A. Young verfasserin aut Stacy Gelhaus Wendell verfasserin aut Greg M. Delgoffe verfasserin aut In Cell Reports Elsevier, 2015 22(2018), 6, Seite 1509-1521 (DE-627)684964562 (DE-600)2649101-1 22111247 nnns volume:22 year:2018 number:6 pages:1509-1521 https://doi.org/10.1016/j.celrep.2018.01.040 kostenfrei https://doaj.org/article/9a323dcf2c784882a7635f4587454ea7 kostenfrei http://www.sciencedirect.com/science/article/pii/S221112471830072X kostenfrei https://doaj.org/toc/2211-1247 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2110 GBV_ILN_2112 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4700 AR 22 2018 6 1509-1521
allfieldsSound	10.1016/j.celrep.2018.01.040 doi (DE-627)DOAJ067872670 (DE-599)DOAJ9a323dcf2c784882a7635f4587454ea7 DE-627 ger DE-627 rakwb eng QH301-705.5 Ashley V. Menk verfasserin aut Early TCR Signaling Induces Rapid Aerobic Glycolysis Enabling Distinct Acute T Cell Effector Functions 2018 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Summary: To fulfill bioenergetic demands of activation, T cells perform aerobic glycolysis, a process common to highly proliferative cells in which glucose is fermented into lactate rather than oxidized in mitochondria. However, the signaling events that initiate aerobic glycolysis in T cells remain unclear. We show T cell activation rapidly induces glycolysis independent of transcription, translation, CD28, and Akt and not involving increased glucose uptake or activity of glycolytic enzymes. Rather, TCR signaling promotes activation of pyruvate dehydrogenase kinase 1 (PDHK1), inhibiting mitochondrial import of pyruvate and facilitating breakdown into lactate. Inhibition of PDHK1 reveals this switch is required acutely for cytokine synthesis but dispensable for cytotoxicity. Functionally, cytokine synthesis is modulated via lactate dehydrogenase, which represses cytokine mRNA translation when aerobic glycolysis is disengaged. Our data provide mechanistic insight to metabolic contribution to effector T cell function and suggest that T cell function may be finely tuned through modulation of glycolytic activity. immunometabolism glycolysis PDHK1 T cell cytokine LDH Biology (General) Nicole E. Scharping verfasserin aut Rebecca S. Moreci verfasserin aut Xue Zeng verfasserin aut Cliff Guy verfasserin aut Sonia Salvatore verfasserin aut Heekyong Bae verfasserin aut Jianxin Xie verfasserin aut Howard A. Young verfasserin aut Stacy Gelhaus Wendell verfasserin aut Greg M. Delgoffe verfasserin aut In Cell Reports Elsevier, 2015 22(2018), 6, Seite 1509-1521 (DE-627)684964562 (DE-600)2649101-1 22111247 nnns volume:22 year:2018 number:6 pages:1509-1521 https://doi.org/10.1016/j.celrep.2018.01.040 kostenfrei https://doaj.org/article/9a323dcf2c784882a7635f4587454ea7 kostenfrei http://www.sciencedirect.com/science/article/pii/S221112471830072X kostenfrei https://doaj.org/toc/2211-1247 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2110 GBV_ILN_2112 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4700 AR 22 2018 6 1509-1521
language	English
source	In Cell Reports 22(2018), 6, Seite 1509-1521 volume:22 year:2018 number:6 pages:1509-1521
sourceStr	In Cell Reports 22(2018), 6, Seite 1509-1521 volume:22 year:2018 number:6 pages:1509-1521
format_phy_str_mv	Article
institution	findex.gbv.de
topic_facet	immunometabolism glycolysis PDHK1 T cell cytokine LDH Biology (General)
isfreeaccess_bool	true
container_title	Cell Reports
authorswithroles_txt_mv	Ashley V. Menk @@aut@@ Nicole E. Scharping @@aut@@ Rebecca S. Moreci @@aut@@ Xue Zeng @@aut@@ Cliff Guy @@aut@@ Sonia Salvatore @@aut@@ Heekyong Bae @@aut@@ Jianxin Xie @@aut@@ Howard A. Young @@aut@@ Stacy Gelhaus Wendell @@aut@@ Greg M. Delgoffe @@aut@@
publishDateDaySort_date	2018-01-01T00:00:00Z
hierarchy_top_id	684964562
id	DOAJ067872670
language_de	englisch
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callnumber-first	Q - Science
author	Ashley V. Menk
spellingShingle	Ashley V. Menk misc QH301-705.5 misc immunometabolism misc glycolysis misc PDHK1 misc T cell misc cytokine misc LDH misc Biology (General) Early TCR Signaling Induces Rapid Aerobic Glycolysis Enabling Distinct Acute T Cell Effector Functions
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topic_title	QH301-705.5 Early TCR Signaling Induces Rapid Aerobic Glycolysis Enabling Distinct Acute T Cell Effector Functions immunometabolism glycolysis PDHK1 T cell cytokine LDH
topic	misc QH301-705.5 misc immunometabolism misc glycolysis misc PDHK1 misc T cell misc cytokine misc LDH misc Biology (General)
topic_unstemmed	misc QH301-705.5 misc immunometabolism misc glycolysis misc PDHK1 misc T cell misc cytokine misc LDH misc Biology (General)
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title	Early TCR Signaling Induces Rapid Aerobic Glycolysis Enabling Distinct Acute T Cell Effector Functions
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title_full	Early TCR Signaling Induces Rapid Aerobic Glycolysis Enabling Distinct Acute T Cell Effector Functions
author_sort	Ashley V. Menk
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author_browse	Ashley V. Menk Nicole E. Scharping Rebecca S. Moreci Xue Zeng Cliff Guy Sonia Salvatore Heekyong Bae Jianxin Xie Howard A. Young Stacy Gelhaus Wendell Greg M. Delgoffe
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author-letter	Ashley V. Menk
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title_sort	early tcr signaling induces rapid aerobic glycolysis enabling distinct acute t cell effector functions
callnumber	QH301-705.5
title_auth	Early TCR Signaling Induces Rapid Aerobic Glycolysis Enabling Distinct Acute T Cell Effector Functions
abstract	Summary: To fulfill bioenergetic demands of activation, T cells perform aerobic glycolysis, a process common to highly proliferative cells in which glucose is fermented into lactate rather than oxidized in mitochondria. However, the signaling events that initiate aerobic glycolysis in T cells remain unclear. We show T cell activation rapidly induces glycolysis independent of transcription, translation, CD28, and Akt and not involving increased glucose uptake or activity of glycolytic enzymes. Rather, TCR signaling promotes activation of pyruvate dehydrogenase kinase 1 (PDHK1), inhibiting mitochondrial import of pyruvate and facilitating breakdown into lactate. Inhibition of PDHK1 reveals this switch is required acutely for cytokine synthesis but dispensable for cytotoxicity. Functionally, cytokine synthesis is modulated via lactate dehydrogenase, which represses cytokine mRNA translation when aerobic glycolysis is disengaged. Our data provide mechanistic insight to metabolic contribution to effector T cell function and suggest that T cell function may be finely tuned through modulation of glycolytic activity.
abstractGer	Summary: To fulfill bioenergetic demands of activation, T cells perform aerobic glycolysis, a process common to highly proliferative cells in which glucose is fermented into lactate rather than oxidized in mitochondria. However, the signaling events that initiate aerobic glycolysis in T cells remain unclear. We show T cell activation rapidly induces glycolysis independent of transcription, translation, CD28, and Akt and not involving increased glucose uptake or activity of glycolytic enzymes. Rather, TCR signaling promotes activation of pyruvate dehydrogenase kinase 1 (PDHK1), inhibiting mitochondrial import of pyruvate and facilitating breakdown into lactate. Inhibition of PDHK1 reveals this switch is required acutely for cytokine synthesis but dispensable for cytotoxicity. Functionally, cytokine synthesis is modulated via lactate dehydrogenase, which represses cytokine mRNA translation when aerobic glycolysis is disengaged. Our data provide mechanistic insight to metabolic contribution to effector T cell function and suggest that T cell function may be finely tuned through modulation of glycolytic activity.
abstract_unstemmed	Summary: To fulfill bioenergetic demands of activation, T cells perform aerobic glycolysis, a process common to highly proliferative cells in which glucose is fermented into lactate rather than oxidized in mitochondria. However, the signaling events that initiate aerobic glycolysis in T cells remain unclear. We show T cell activation rapidly induces glycolysis independent of transcription, translation, CD28, and Akt and not involving increased glucose uptake or activity of glycolytic enzymes. Rather, TCR signaling promotes activation of pyruvate dehydrogenase kinase 1 (PDHK1), inhibiting mitochondrial import of pyruvate and facilitating breakdown into lactate. Inhibition of PDHK1 reveals this switch is required acutely for cytokine synthesis but dispensable for cytotoxicity. Functionally, cytokine synthesis is modulated via lactate dehydrogenase, which represses cytokine mRNA translation when aerobic glycolysis is disengaged. Our data provide mechanistic insight to metabolic contribution to effector T cell function and suggest that T cell function may be finely tuned through modulation of glycolytic activity.
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title_short	Early TCR Signaling Induces Rapid Aerobic Glycolysis Enabling Distinct Acute T Cell Effector Functions
url	https://doi.org/10.1016/j.celrep.2018.01.040 https://doaj.org/article/9a323dcf2c784882a7635f4587454ea7 http://www.sciencedirect.com/science/article/pii/S221112471830072X https://doaj.org/toc/2211-1247
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author2	Nicole E. Scharping Rebecca S. Moreci Xue Zeng Cliff Guy Sonia Salvatore Heekyong Bae Jianxin Xie Howard A. Young Stacy Gelhaus Wendell Greg M. Delgoffe
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up_date	2024-07-03T14:34:10.277Z
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Early TCR Signaling Induces Rapid Aerobic Glycolysis Enabling Distinct Acute T Cell Effector Functions

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