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

Publication ,  Journal Article
Michalek, RD; Gerriets, VA; Jacobs, SR; Macintyre, AN; MacIver, NJ; Mason, EF; Sullivan, SA; Nichols, AG; Rathmell, JC
Published in: J Immunol
March 15, 2011

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.

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Published In

J Immunol

DOI

EISSN

1550-6606

Publication Date

March 15, 2011

Volume

186

Issue

6

Start / End Page

3299 / 3303

Location

United States

Related Subject Headings

  • TOR Serine-Threonine Kinases
  • T-Lymphocytes, Regulatory
  • T-Lymphocytes, Helper-Inducer
  • T-Lymphocyte Subsets
  • Mice, Transgenic
  • Mice, Inbred C57BL
  • Mice
  • Lipid Peroxidation
  • Immunophenotyping
  • Immunology
 

Citation

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Michalek, R. D., Gerriets, V. A., Jacobs, S. R., Macintyre, A. N., MacIver, N. J., Mason, E. F., … Rathmell, J. C. (2011). Cutting edge: distinct glycolytic and lipid oxidative metabolic programs are essential for effector and regulatory CD4+ T cell subsets. Journal of Immunology (Baltimore, Md. : 1950), 186(6), 3299–3303. https://doi.org/10.4049/jimmunol.1003613
Michalek, Ryan D., Valerie A. Gerriets, Sarah R. Jacobs, Andrew N. Macintyre, Nancie J. MacIver, Emily F. Mason, Sarah A. Sullivan, Amanda G. Nichols, and Jeffrey C. Rathmell. “Cutting edge: distinct glycolytic and lipid oxidative metabolic programs are essential for effector and regulatory CD4+ T cell subsets.Journal of Immunology (Baltimore, Md. : 1950) 186, no. 6 (March 2011): 3299–3303. https://doi.org/10.4049/jimmunol.1003613.
Michalek RD, Gerriets VA, Jacobs SR, Macintyre AN, MacIver NJ, Mason EF, et al. Cutting edge: distinct glycolytic and lipid oxidative metabolic programs are essential for effector and regulatory CD4+ T cell subsets. Journal of immunology (Baltimore, Md : 1950). 2011 Mar;186(6):3299–303.
Michalek, Ryan D., et al. “Cutting edge: distinct glycolytic and lipid oxidative metabolic programs are essential for effector and regulatory CD4+ T cell subsets.Journal of Immunology (Baltimore, Md. : 1950), vol. 186, no. 6, Mar. 2011, pp. 3299–303. Epmc, doi:10.4049/jimmunol.1003613.
Michalek RD, Gerriets VA, Jacobs SR, Macintyre AN, MacIver NJ, Mason EF, Sullivan SA, Nichols AG, Rathmell JC. Cutting edge: distinct glycolytic and lipid oxidative metabolic programs are essential for effector and regulatory CD4+ T cell subsets. Journal of immunology (Baltimore, Md : 1950). 2011 Mar;186(6):3299–3303.

Published In

J Immunol

DOI

EISSN

1550-6606

Publication Date

March 15, 2011

Volume

186

Issue

6

Start / End Page

3299 / 3303

Location

United States

Related Subject Headings

  • TOR Serine-Threonine Kinases
  • T-Lymphocytes, Regulatory
  • T-Lymphocytes, Helper-Inducer
  • T-Lymphocyte Subsets
  • Mice, Transgenic
  • Mice, Inbred C57BL
  • Mice
  • Lipid Peroxidation
  • Immunophenotyping
  • Immunology