Metabolic programming and PDHK1 control CD4+ T cell subsets and inflammation

Activation of CD4+ T cells results in rapid proliferation and differentiation into effector and regulatory subsets. CD4+ effector T cell (Teff) (Th1 and Th17) and Treg subsets are metabolically distinct, yet the specific metabolic differences that modify T cell populations are uncertain. Here, we evaluated CD4+ T cell populations in murine models and determined that inflammatory Teffs maintain high expression of glycolytic genes and rely on high glycolytic rates, while Tregs are oxidative and require mitochondrial electron transport to proliferate, differentiate, and survive. Metabolic profiling revealed that pyruvate dehydrogenase (PDH) is a key bifurcation point between T cell glycolytic and oxidative…

• NM
  National Multiple Sclerosis Society
• CA
  Crohn's and Colitis Foundation of America
• LA
  Leukemia and Lymphoma Society
• KR
  Kenneth Rainin Foundation
• CA
  Crohn's and Colitis Foundation
• LR
  Lupus Research Alliance
• MS
  Multiple Sclerosis Society
• NI
  National Institutes of Health

  Awards: R01HL108006, R00CA168997, R01AI110613