Foxp3 reprograms T cell metabolism to function in low glucose high lactate environments

By A. Angelin, Luis Gil-de-Gómez, Satinder Dahiya, Jing Jiao, Lili Guo, M. Levine, Zhonglin Wang, W. Quinn, P. Kopinski, Liqing Wang and 10 more. Cell Metabolism, 2017

1,112 citations recorded by the source corpus.

Summary 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 (Treg) maintain peripheral tolerance, but how Treg 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 Treg a metabolic advantage in low glucose, lactate rich environments; resisting 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.

Subfields: Immunology, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/e6af25b496e95a67e46f18981152a57afcc11a49

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Citations in the corpus

The updated landscape of tumor microenvironment and drug repurposing (2020, background): “The expression of Foxp3 suppresses Myc and glycolysis to promote the survival of Treg in a high lactate microenvironment, thereby providing a supportive immunosuppressive microenvironment for cancer cells.(79) Lactate promotes angiogenesis and the survival of hypoxic cells and induces an acidic micr”
Monocyte-Macrophages and T Cells in Atherosclerosis (2017, positive): “This state allows Treg cells to function in low-glucose, lactaterich environments that impair Teff cell function and proliferation (Angelin et al., 2017).”
Mitochondrial metabolism and cancer (2017, background): “Intriguingly, a similar metabolic profile is also displayed by immunosuppressive cell types including CD4CD25FOXP3 regulatory T cells and myeloid-derived suppressor cells [214, 215], which presumably renders them less sensitive to metabolic competition for glucose within them tumor microenvironment.”