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Anti-inflammatory effect of IL-10 mediated by metabolic reprogramming of macrophages.
Ip, W K Eddie; Hoshi, Namiko; Shouval, Dror S; Snapper, Scott; Medzhitov, Ruslan.
Afiliación
  • Ip WKE; Department of Immunobiology and Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT 06510, USA.
  • Hoshi N; Department of Immunobiology and Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT 06510, USA.
  • Shouval DS; Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA.
  • Snapper S; Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA.
  • Medzhitov R; Department of Immunobiology and Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT 06510, USA. ruslan.medzhitov@yale.edu.
Science ; 356(6337): 513-519, 2017 05 05.
Article en En | MEDLINE | ID: mdl-28473584
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-1ß.
Asunto(s)

Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Enfermedades Inflamatorias del Intestino / Interleucina-10 / Colitis / Intestinos / Macrófagos Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: Science Año: 2017 Tipo del documento: Article País de afiliación: Estados Unidos

Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Enfermedades Inflamatorias del Intestino / Interleucina-10 / Colitis / Intestinos / Macrófagos Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: Science Año: 2017 Tipo del documento: Article País de afiliación: Estados Unidos