HIF1α–dependent glycolytic pathway orchestrates a metabolic checkpoint for the differentiation of TH17 and Treg cells

By L. Shi, Ruoning Wang, Gonghua Huang, P. Vogel, G. Neale, Douglas R. Green, Hongbo Chi. Journal of Experimental Medicine, 2011

1,604 citations recorded by the source corpus.

HIF1α induction by mTOR represents a metabolic checkpoint for the differentiation of TH17 and Treg cells.

Subfields: Cancer Research, Immunology

View Paper: https://www.semanticscholar.org/paper/5a73a96520b9f5f0f4272d3e2bf5acb7abdad655

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Citations in the corpus

Metabolic Instruction of Immunity (2017, positive): “Dampening glycolysis through deletion of HIF-1α or with the inhibitor 2-DG in T cells impairs Th17 development and instead promotes Treg cells, even under Th17-inducing culture conditions (Dang et al., 2011; Shi et al., 2011).”
Metabolic Regulation of T Lymphocytes (2013, background): “HIF-1α plays a key role in T cell fate at this stage, as HIF-1α deficiency suppressed Th17 and instead increased Treg development (30, 90).”
The transcription factor Myc controls metabolic reprogramming upon T lymphocyte activation (2011, methodology): “To further test the dependency of T cell proliferation on glucose and glutamine catabolism in vivo, we applied 2DG and DON in an adoptive transfer model by using ovalbumin (OVA)specific, TCR-transgenic OT-II T cells (Figure 1G; Shi et al., 2011).”
The Glucose Transporter Glut1 is Selectively Essential for CD4 T Cell Activation and Effector Function (2014, neutral): “…Is Required for the Generation of Teff, but Not nTreg or iTreg We and others have previously shown in vitro that murine Teff cells (Th1, Th2, and Th17) utilize a highly glycolytic metabolism, while Treg cells are primarily oxidative and use lipids as fuel (Michalek et al., 2011a; Shi et al., 2011).”
Development and maintenance of regulatory T cells. (2013, background): “a central regulator of cellular metabolism (Shi et al., 2011).”
Mitochondria in the regulation of innate and adaptive immunity (2015, positive): “Pharmacologic and genetic inhibition of the enzyme acetyl-CoA carboxylase 1 (ACC1), the enzyme that catalyzes the first step of de novo fatty-acid synthesis, impaired Th17 cell differentiation, and promoted Tregs in vitro and in vivo, as well as attenuated EAE in mice (Berod et al., 2014).”
MYC on the Path to Cancer (2012, background): “It was also documented that HIF-1, which regulates anaerobic glycolysis, was not required for cell growth but required for T cell fate determination (Dang et al., 2011; Shi et al., 2011).”
Gut Microbial Metabolites Fuel Host Antibody Responses. (2016, background): “We observed elevated levels of cellular acetyl-CoA and lipid droplets, which promote B cell differentiation and antibody production. mTOR activation increases glycolytic activity in general (Masui et al., 2013; Shi et al., 2011).”
Control of T(H)17/T(reg) balance by hypoxia-inducible factor 1. (2011, neutral): “(Shi et al., 2011) on the mTOR pathway”
Lactate Regulates Metabolic and Pro-inflammatory Circuits in Control of T Cell Migration and Effector Functions (2015, background): “Previous reports have shown that HIFinduced glycolysis is necessary to promote the differentiation of naïve CD4 T cells toward the Th17 subset [45].”
HIF Transcription Factors, Inflammation, and Immunity (2014, background): “…and less OXPHOS than in-vitro-induced T regulatory cells, which show a greater reliance on lipid oxidation and OXPHOS (Michalek et al., 2011; Shi et al., 2011 Review of CD4 + Th17 producing cells in vitro and in MOG/CFA-induced experimental autoimmune encephalomyelitis (EAE) (Dang et al.,…”
Normalization of CD4+ T Cell Metabolism Reverses Lupus (2015, background): “Glycolysis is critical for T cell effector functions, and increased glycolysis leads to autoimmunity (13, 17).”