Cutting edge: distinct glycolytic and lipid oxidative metabolic programs are essential for effector and regulatory CD4+ T cell subsets.
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Stimulated CD4(+) T lymphocytes can differentiate into effector T cell (Teff) or inducible regulatory T cell (Treg) subsets with specific immunological roles. We show that Teff and Treg require distinct metabolic programs to support these functions. Th1, Th2, and Th17 cells expressed high surface levels of the glucose transporter Glut1 and were highly glycolytic. Treg, in contrast, expressed low levels of Glut1 and had high lipid oxidation rates. Consistent with glycolysis and lipid oxidation promoting Teff and Treg, respectively, Teff were selectively increased in Glut1 transgenic mice and reliant on glucose metabolism, whereas Treg had activated AMP-activated protein kinase and were dependent on lipid oxidation. Importantly, AMP-activated protein kinase stimulation was sufficient to decrease Glut1 and increase Treg generation in an asthma model. These data demonstrate that CD4(+) T cell subsets require distinct metabolic programs that can be manipulated in vivo to control Treg and Teff development in inflammatory diseases.
SubjectAMP-Activated Protein Kinases
Disease Models, Animal
Glucose Transporter Type 1
Mice, Inbred C57BL
TOR Serine-Threonine Kinases
Published Version (Please cite this version)10.4049/jimmunol.1003613
Publication InfoMichalek, Ryan D; Gerriets, Valerie A; Jacobs, Sarah R; Macintyre, Andrew N; MacIver, Nancie J; Mason, Emily F; ... Rathmell, Jeffrey C (2011). Cutting edge: distinct glycolytic and lipid oxidative metabolic programs are essential for effector and regulatory CD4+ T cell subsets. J Immunol, 186(6). pp. 3299-3303. 10.4049/jimmunol.1003613. Retrieved from https://hdl.handle.net/10161/10317.
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Associate Professor of Pediatrics
My laboratory is broadly interested in how large changes in nutritional status (e.g. malnutrition or obesity) influence T cell immunity. Malnutrition can lead to immunodeficiency and increased risk of infection, whereas obesity is associated with inflammation that promotes multiple diseases including autoimmunity, type 2 diabetes, and cardiovascular disease. We have identified the adipocyte-secreted hormone leptin as a critical link between nutrition and immunity. Leptin is
Assistant Professor of Medicine
Adjunct Associate Professor in the Department of Pharmacology and Cancer Biology
My laboratory studies the mechanisms and role of glucose metabolism in lymphocyte survival and activation. We have found that dramatic increases in glucose metabolism are necessary for lymphocytes to survive and mount immune responses. Excessive glucose metabolism, however, can lead to T cell hyperactivation and autoimmunity. A key mechanism for control of lymphocyte glucose metabolism is regulation of glucose uptake by the glucose transporter, Glut1. Interestingly, upregulation of Glut1
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