6-Phosphogluconate dehydrogenase (6PGD), a key checkpoint in reprogramming of regulatory T cells metabolism and function

Cellular metabolism has key roles in T cells differentiation and function. CD4+ T helper-1 (Th1), Th2, and Th17 subsets are highly glycolytic while regulatory T cells (Tregs) use glucose during expansion but rely on fatty acid oxidation for function. Upon uptake, glucose can enter pentose phosphate...

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Autores principales:	Saeed Daneshmandi, Teresa Cassel, Richard M Higashi, Teresa W-M Fan, Pankaj Seth
Formato:	article
Lenguaje:	EN
Publicado:	eLife Sciences Publications Ltd 2021
Materias:	regulatory T cell metabolism 6PGD immunoregulation glucose pentose phosphate pathway Medicine R Science Q Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/851c6bd2a26549a4b642403b49029a4d
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spelling	oai:doaj.org-article:851c6bd2a26549a4b642403b49029a4d2021-11-15T06:05:32Z6-Phosphogluconate dehydrogenase (6PGD), a key checkpoint in reprogramming of regulatory T cells metabolism and function10.7554/eLife.674762050-084Xe67476https://doaj.org/article/851c6bd2a26549a4b642403b49029a4d2021-10-01T00:00:00Zhttps://elifesciences.org/articles/67476https://doaj.org/toc/2050-084XCellular metabolism has key roles in T cells differentiation and function. CD4+ T helper-1 (Th1), Th2, and Th17 subsets are highly glycolytic while regulatory T cells (Tregs) use glucose during expansion but rely on fatty acid oxidation for function. Upon uptake, glucose can enter pentose phosphate pathway (PPP) or be used in glycolysis. Here, we showed that blocking 6-phosphogluconate dehydrogenase (6PGD) in the oxidative PPP resulted in substantial reduction of Tregs suppressive function and shifts toward Th1, Th2, and Th17 phenotypes which led to the development of fetal inflammatory disorder in mice model. These in turn improved anti-tumor responses and worsened the outcomes of colitis model. Metabolically, 6PGD blocked Tregs showed improved glycolysis and enhanced non-oxidative PPP to support nucleotide biosynthesis. These results uncover critical role of 6PGD in modulating Tregs plasticity and function, which qualifies it as a novel metabolic checkpoint for immunotherapy applications.Saeed DaneshmandiTeresa CasselRichard M HigashiTeresa W-M FanPankaj SetheLife Sciences Publications Ltdarticleregulatory T cellmetabolism6PGDimmunoregulationglucosepentose phosphate pathwayMedicineRScienceQBiology (General)QH301-705.5ENeLife, Vol 10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	regulatory T cell metabolism 6PGD immunoregulation glucose pentose phosphate pathway Medicine R Science Q Biology (General) QH301-705.5
spellingShingle	regulatory T cell metabolism 6PGD immunoregulation glucose pentose phosphate pathway Medicine R Science Q Biology (General) QH301-705.5 Saeed Daneshmandi Teresa Cassel Richard M Higashi Teresa W-M Fan Pankaj Seth 6-Phosphogluconate dehydrogenase (6PGD), a key checkpoint in reprogramming of regulatory T cells metabolism and function
description	Cellular metabolism has key roles in T cells differentiation and function. CD4+ T helper-1 (Th1), Th2, and Th17 subsets are highly glycolytic while regulatory T cells (Tregs) use glucose during expansion but rely on fatty acid oxidation for function. Upon uptake, glucose can enter pentose phosphate pathway (PPP) or be used in glycolysis. Here, we showed that blocking 6-phosphogluconate dehydrogenase (6PGD) in the oxidative PPP resulted in substantial reduction of Tregs suppressive function and shifts toward Th1, Th2, and Th17 phenotypes which led to the development of fetal inflammatory disorder in mice model. These in turn improved anti-tumor responses and worsened the outcomes of colitis model. Metabolically, 6PGD blocked Tregs showed improved glycolysis and enhanced non-oxidative PPP to support nucleotide biosynthesis. These results uncover critical role of 6PGD in modulating Tregs plasticity and function, which qualifies it as a novel metabolic checkpoint for immunotherapy applications.
format	article
author	Saeed Daneshmandi Teresa Cassel Richard M Higashi Teresa W-M Fan Pankaj Seth
author_facet	Saeed Daneshmandi Teresa Cassel Richard M Higashi Teresa W-M Fan Pankaj Seth
author_sort	Saeed Daneshmandi
title	6-Phosphogluconate dehydrogenase (6PGD), a key checkpoint in reprogramming of regulatory T cells metabolism and function
title_short	6-Phosphogluconate dehydrogenase (6PGD), a key checkpoint in reprogramming of regulatory T cells metabolism and function
title_full	6-Phosphogluconate dehydrogenase (6PGD), a key checkpoint in reprogramming of regulatory T cells metabolism and function
title_fullStr	6-Phosphogluconate dehydrogenase (6PGD), a key checkpoint in reprogramming of regulatory T cells metabolism and function
title_full_unstemmed	6-Phosphogluconate dehydrogenase (6PGD), a key checkpoint in reprogramming of regulatory T cells metabolism and function
title_sort	6-phosphogluconate dehydrogenase (6pgd), a key checkpoint in reprogramming of regulatory t cells metabolism and function
publisher	eLife Sciences Publications Ltd
publishDate	2021
url	https://doaj.org/article/851c6bd2a26549a4b642403b49029a4d
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6-Phosphogluconate dehydrogenase (6PGD), a key checkpoint in reprogramming of regulatory T cells metabolism and function

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