| First Author | Ip WKE | Year | 2017 |
| Journal | Science | Volume | 356 |
| Issue | 6337 | Pages | 513-519 |
| PubMed ID | 28473584 | Mgi Jnum | J:243289 |
| Mgi Id | MGI:5908058 | Doi | 10.1126/science.aal3535 |
| Citation | Ip WKE, et al. (2017) Anti-inflammatory effect of IL-10 mediated by metabolic reprogramming of macrophages. Science 356(6337):513-519 |
| abstractText | 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-1beta. |
