Cutting edge: distinct glycolytic and lipid oxidative metabolic programs are essential for effector and regulatory CD4+ T cell subsets.

dc.contributor.author

Michalek, Ryan D

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Gerriets, Valerie A

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Jacobs, Sarah R

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Macintyre, Andrew N

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MacIver, Nancie J

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Mason, Emily F

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Sullivan, Sarah A

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Nichols, Amanda G

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Rathmell, Jeffrey C

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United States

dc.date.accessioned

2015-07-16T19:03:07Z

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2011-03-15

dc.description.abstract

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.

dc.identifier

http://www.ncbi.nlm.nih.gov/pubmed/21317389

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jimmunol.1003613

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1550-6606

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https://hdl.handle.net/10161/10317

dc.language

eng

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The American Association of Immunologists

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J Immunol

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10.4049/jimmunol.1003613

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AMP-Activated Protein Kinases

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Animals

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Asthma

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Cell Survival

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Cells, Cultured

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Disease Models, Animal

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Glucose Transporter Type 1

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Glycolysis

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Immunophenotyping

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Lipid Peroxidation

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Mice

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Mice, Inbred C57BL

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Mice, Transgenic

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T-Lymphocyte Subsets

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T-Lymphocytes, Helper-Inducer

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T-Lymphocytes, Regulatory

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TOR Serine-Threonine Kinases

dc.title

Cutting edge: distinct glycolytic and lipid oxidative metabolic programs are essential for effector and regulatory CD4+ T cell subsets.

dc.type

Journal article

duke.contributor.orcid

Macintyre, Andrew N|0000-0002-5297-0207

duke.contributor.orcid

MacIver, Nancie J|0000-0003-3676-9391

pubs.author-url

http://www.ncbi.nlm.nih.gov/pubmed/21317389

pubs.begin-page

3299

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3303

pubs.issue

6

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Basic Science Departments

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Clinical Science Departments

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Duke

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Duke Molecular Physiology Institute

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Immunology

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Institutes and Centers

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Pediatrics

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Pediatrics, Endocrinology

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Pharmacology & Cancer Biology

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Sarah Stedman Nutrition & Metabolism Center

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School of Medicine

pubs.publication-status

Published

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186

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