6-phosphogluconate dehydrogenase (6pgd), a key checkpoint in reprogramming of regulatory t cells metabolism and function

Saeed Daneshmandi, Teresa Cassel, Richard M. Higashi, Teresa W.M. Fan, Pankaj Seth

Research output: Contribution to journalArticlepeer-review

23 Scopus citations

Abstract

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.

Original languageEnglish
Article numbere67476
JournaleLife
Volume10
DOIs
StatePublished - Oct 2021

Bibliographical note

Publisher Copyright:
‍© Daneshmandi et al.

ASJC Scopus subject areas

  • General Neuroscience
  • General Biochemistry, Genetics and Molecular Biology
  • General Immunology and Microbiology

Fingerprint

Dive into the research topics of '6-phosphogluconate dehydrogenase (6pgd), a key checkpoint in reprogramming of regulatory t cells metabolism and function'. Together they form a unique fingerprint.

Cite this