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PD-1 alters T-cell metabolic reprogramming by inhibiting glycolysis and promoting lipolysis and fatty acid oxidation.

Publication ,  Journal Article
Patsoukis, N; Bardhan, K; Chatterjee, P; Sari, D; Liu, B; Bell, LN; Karoly, ED; Freeman, GJ; Petkova, V; Seth, P; Li, L; Boussiotis, VA
Published in: Nature communications
March 2015

During activation, T cells undergo metabolic reprogramming, which imprints distinct functional fates. We determined that on PD-1 ligation, activated T cells are unable to engage in glycolysis or amino acid metabolism but have an increased rate of fatty acid β-oxidation (FAO). PD-1 promotes FAO of endogenous lipids by increasing expression of CPT1A, and inducing lipolysis as indicated by elevation of the lipase ATGL, the lipolysis marker glycerol and release of fatty acids. Conversely, CTLA-4 inhibits glycolysis without augmenting FAO, suggesting that CTLA-4 sustains the metabolic profile of non-activated cells. Because T cells utilize glycolysis during differentiation to effectors, our findings reveal a metabolic mechanism responsible for PD-1-mediated blockade of T-effector cell differentiation. The enhancement of FAO provides a mechanistic explanation for the longevity of T cells receiving PD-1 signals in patients with chronic infections and cancer, and for their capacity to be reinvigorated by PD-1 blockade.

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Published In

Nature communications

DOI

EISSN

2041-1723

ISSN

2041-1723

Publication Date

March 2015

Volume

6

Start / End Page

6692

Related Subject Headings

  • Programmed Cell Death 1 Receptor
  • Oxidation-Reduction
  • Lymphocyte Activation
  • Lipolysis
  • Lipid Metabolism
  • In Vitro Techniques
  • Humans
  • Glycolysis
  • Fatty Acids
  • Cells, Cultured
 

Citation

APA
Chicago
ICMJE
MLA
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Patsoukis, N., Bardhan, K., Chatterjee, P., Sari, D., Liu, B., Bell, L. N., … Boussiotis, V. A. (2015). PD-1 alters T-cell metabolic reprogramming by inhibiting glycolysis and promoting lipolysis and fatty acid oxidation. Nature Communications, 6, 6692. https://doi.org/10.1038/ncomms7692
Patsoukis, Nikolaos, Kankana Bardhan, Pranam Chatterjee, Duygu Sari, Bianling Liu, Lauren N. Bell, Edward D. Karoly, et al. “PD-1 alters T-cell metabolic reprogramming by inhibiting glycolysis and promoting lipolysis and fatty acid oxidation.Nature Communications 6 (March 2015): 6692. https://doi.org/10.1038/ncomms7692.
Patsoukis N, Bardhan K, Chatterjee P, Sari D, Liu B, Bell LN, et al. PD-1 alters T-cell metabolic reprogramming by inhibiting glycolysis and promoting lipolysis and fatty acid oxidation. Nature communications. 2015 Mar;6:6692.
Patsoukis, Nikolaos, et al. “PD-1 alters T-cell metabolic reprogramming by inhibiting glycolysis and promoting lipolysis and fatty acid oxidation.Nature Communications, vol. 6, Mar. 2015, p. 6692. Epmc, doi:10.1038/ncomms7692.
Patsoukis N, Bardhan K, Chatterjee P, Sari D, Liu B, Bell LN, Karoly ED, Freeman GJ, Petkova V, Seth P, Li L, Boussiotis VA. PD-1 alters T-cell metabolic reprogramming by inhibiting glycolysis and promoting lipolysis and fatty acid oxidation. Nature communications. 2015 Mar;6:6692.

Published In

Nature communications

DOI

EISSN

2041-1723

ISSN

2041-1723

Publication Date

March 2015

Volume

6

Start / End Page

6692

Related Subject Headings

  • Programmed Cell Death 1 Receptor
  • Oxidation-Reduction
  • Lymphocyte Activation
  • Lipolysis
  • Lipid Metabolism
  • In Vitro Techniques
  • Humans
  • Glycolysis
  • Fatty Acids
  • Cells, Cultured