Differential Reliance on Lipid Metabolism as a Salvage Pathway Underlies Functional Differences of T Cell Subsets in Poor Nutrient Environments
| Autor: | Ian A. Blair, Evan R. Zynda, Maria Torres-Castillo, Sarya Mansour, James L. Riley, Jennifer L. Donato, Angel Varela-Rohena, Stefana Voicu, Lili Guo, Christopher Ecker, Jackie Pajda, Luis E. Cortina, Andrew Medvec, Luis Gil-de-Gómez, Melanie Andolina, Pei-Yi Lin |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
CD4-Positive T-Lymphocytes
0301 basic medicine Naive T cell Glutamine T cell Lymphocyte Activation Article Antibodies Oxidative Phosphorylation General Biochemistry Genetics and Molecular Biology Interferon-gamma 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine T-Lymphocyte Subsets Lipid droplet medicine Humans lcsh:QH301-705.5 Cells Cultured Fatty acid synthesis Glutaminolysis Fatty acid metabolism Receptors IgE Effector Fatty Acids Lipid metabolism Lipid Metabolism Cell biology Glucose 030104 developmental biology medicine.anatomical_structure chemistry lcsh:Biology (General) Tetradecanoylphorbol Acetate Immunologic Memory 030215 immunology |
| Zdroj: | Cell Reports, Vol 23, Iss 3, Pp 741-755 (2018) Cell reports |
| ISSN: | 2211-1247 |
| Popis: | SUMMARY T cells compete with malignant cells for limited nutrients within the solid tumor microenvironment. We found that effector memory CD4 T cells respond distinctly from other T cell subsets to limiting glucose and can maintain high levels of interferon-γ (IFN-γ) production in a nutrient-poor environment. Unlike naive (TN) or central memory T (TCM) cells, effector memory T (TEM) cells fail to upregulate fatty acid synthesis, oxidative phosphorylation, and reductive glutaminolysis in limiting glucose. Interference of fatty acid synthesis in naive T cells dramatically upregulates IFN-γ, while increasing exogenous lipids in media inhibits production of IFN-γ by all subsets, suggesting that relative ratio of fatty acid metabolism to glycolysis is a direct predictor of T cell effector activity. Together, these data suggest that effector memory T cells are programmed to have limited ability to synthesize and metabolize fatty acids, which allows them to maintain T cell function in nutrient-depleted microenvironments. In Brief Ecker et al. distinguish unique metabolic and functional properties of naive and memory T cell subsets during glucose limitation. During glucose starvation, T cells begin to differentially rely on fatty acid synthesis and glutamine utilization to survive. Unexpectedly, reliance on fatty acid synthesis alters the ability to produce IFN-γ. |
| Databáze: | OpenAIRE |
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