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

Wai Kee Eddie Ip, Namiko Hoshi, Dror S. Shouval, Scott Snapper, Ruslan Medzhitov

Research output: Contribution to journalArticle

246 Scopus citations

Abstract

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 species. In the absence of IL-10 signaling, macrophages accumulate damaged mitochondria in a mouse model of colitis and inflammatory bowel disease patients, and this results in dysregulated activation of the NLRP3 inflammasome and production of IL-1β.

Original languageEnglish (US)
Pages (from-to)513-519
Number of pages7
JournalScience
Volume356
Issue number6337
DOIs
StatePublished - May 5 2017
Externally publishedYes

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