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Foxp3 Reprograms T Cell Metabolism to Function in Low-Glucose, High-Lactate Environments.

Cell metabolism | Jun 6, 2017

Immune cells function in diverse metabolic environments. Tissues with low glucose and high lactate concentrations, such as the intestinal tract or ischemic tissues, frequently require immune responses to be more pro-tolerant, avoiding unwanted reactions against self-antigens or commensal bacteria. T-regulatory cells (Tregs) maintain peripheral tolerance, but how Tregs function in low-glucose, lactate-rich environments is unknown. We report that the Treg transcription factor Foxp3 reprograms T cell metabolism by suppressing Myc and glycolysis, enhancing oxidative phosphorylation, and increasing nicotinamide adenine dinucleotide oxidation. These adaptations allow Tregs a metabolic advantage in low-glucose, lactate-rich environments; they resist lactate-mediated suppression of T cell function and proliferation. This metabolic phenotype may explain how Tregs promote peripheral immune tolerance during tissue injury but also how cancer cells evade immune destruction in the tumor microenvironment. Understanding Treg metabolism may therefore lead to novel approaches for selective immune modulation in cancer and autoimmune diseases.

Pubmed ID: 28416194 RIS Download

Mesh terms: Animals | Cell Line | Cellular Microenvironment | Cellular Reprogramming | Forkhead Transcription Factors | Glucose | Glycolysis | Humans | Lactic Acid | Mice | Mice, Inbred BALB C | Mice, Knockout | Oxidative Phosphorylation | Proto-Oncogene Proteins c-myc | T-Lymphocytes, Regulatory

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Associated grants

  • Agency: NIDDK NIH HHS, Id: K23 DK101600
  • Agency: NIDDK NIH HHS, Id: R01 DK098656
  • Agency: NIMH NIH HHS, Id: R01 MH108592
  • Agency: NIDDK NIH HHS, Id: R01 DK106243
  • Agency: NIDDK NIH HHS, Id: K08 DK092282
  • Agency: NIAID NIH HHS, Id: P01 AI073489
  • Agency: NIAID NIH HHS, Id: K08 AI095353
  • Agency: NIAID NIH HHS, Id: R56 AI095276
  • Agency: NCI NIH HHS, Id: P30 CA016520
  • Agency: NIH HHS, Id: R01 OD010944
  • Agency: NIAID NIH HHS, Id: R01 AI073938
  • Agency: NIDDK NIH HHS, Id: P30 DK019525
  • Agency: NINDS NIH HHS, Id: R01 NS021328
  • Agency: NCI NIH HHS, Id: R33 CA182384

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