Anti-inflammatory effect of IL-10 mediated by metabolic reprogramming of macrophages

Interleukin 10 (IL-10) is an anti-inflammatory cytokine that plays a critical role in the control of immune responses. However, its mechanisms of action remain poorly understood. Here, we show that IL-10 opposes the switch to the metabolic program induced by inflammatory stimuli in macrophages. Specifically, we show that IL-10 inhibits lipopolysaccharide-induced glucose uptake and glycolysis and promotes oxidative phosphorylation. Furthermore, IL-10 suppresses mammalian target of rapamycin (mTOR) activity through the induction of an mTOR inhibitor, DDIT4. Consequently, IL-10 promotes mitophagy that eliminates dysfunctional mitochondria characterized by low membrane potential and a high level of reactive oxygen…

• HH
  Howard Hughes Medical Institute

  Award: award301959
• LM
  Leona M. and Harry B. Helmsley Charitable Trust

  Award: award293655
• BF
  Blavatnik Family Foundation

  Award: award301960
• EK
  Else Kröner-Fresenius-Stiftung

  Award: award301958
• NI
  National Institutes of Health

  Awards: AI046688, DK071754, CA157461, award301957