Normalization of CD4 + T cell metabolism reverses lupus

Systemic lupus erythematosus (SLE) is an autoimmune disease in which autoreactive CD4(+) T cells play an essential role. CD4(+) T cells rely on glycolysis for inflammatory effector functions, but recent studies have shown that mitochondrial metabolism supports their chronic activation. How these processes contribute to lupus is unclear. We show that both glycolysis and mitochondrial oxidative metabolism are elevated in CD4(+) T cells from lupus-prone B6.Sle1.Sle2.Sle3 (TC) mice as compared to non-autoimmune controls. In vitro, both the mitochondrial metabolism inhibitor metformin and the glucose metabolism inhibitor 2-deoxy-d-glucose (2DG) reduced interferon-γ (IFN-γ) production, although at different stages…

• JD
  Juvenile Diabetes Research Foundation United States of America

  Award: CDA 2-2012-280
• NI
  National Institutes of Health

  Awards: ALR-TIL 0000075018, R01 AI045050, P01 AI42288