Anti-inflammatory Effect of IL-10 Mediated by Metabolic Reprogramming of Macrophages

Overview

Journal Science

Specialty Science

Date 2017 May 6

PMID 28473584

Citations 574

Authors

W K Eddie Ip

Namiko Hoshi

Dror S Shouval

Scott Snapper

Ruslan Medzhitov

Affiliations

Soon will be listed here.

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.

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