The STAT3–IL-10–IL-6 Pathway Is a Novel Regulator of Macrophage Efferocytosis and Phenotypic Conversion in Sterile Liver Injury

Lara Campana, Philip J Starkey Lewis, Antonella Pellicoro, Rebecca L Aucott, Janet Man, Eoghan O'Duibhir, Sarah E Mok, Sofia Ferreira-Gonzalez, Eilidh Livingstone, Stephen N Greenhalgh, Katherine L Hull, Douglas Vernimmen, Neil C Henderson, Luke Boulter, Christopher D Gregory, Yi Feng, Stephen M Anderton, Stuart J Forbes, John P Iredale

Research output: Contribution to journalArticle (Academic Journal)peer-review

33 Citations (Scopus)

Abstract

The disposal of apoptotic bodies by professional phagocytes is crucial to effective inflammation resolution. Our ability to improve the disposal of apoptotic bodies by professional phagocytes is impaired by a limited understanding of the molecular mechanisms that regulate the engulfment and digestion of the efferocytic cargo. Macrophages are professional phagocytes necessary for liver inflammation, fibrosis, and resolution, switching their phenotype from proinflammatory to restorative. Using sterile liver injury models, we show that the STAT3–IL-10–IL-6 axis is a positive regulator of macrophage efferocytosis, survival, and phenotypic conversion, directly linking debris engulfment to tissue repair.
Original languageEnglish
Pages (from-to)1169-1187
Number of pages19
JournalJournal of Immunology
Volume200
Issue number3
Early online date22 Jan 2018
DOIs
Publication statusPublished - 1 Feb 2018

Bibliographical note

Copyright © 2018 by The American Association of Immunologists, Inc.

Keywords

  • Adoptive Transfer
  • Animals
  • Apoptosis/immunology
  • Humans
  • Interleukin-10/metabolism
  • Interleukin-6/metabolism
  • Liver/injuries
  • Liver Cirrhosis/pathology
  • Macrophages/immunology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Necrosis/immunology
  • Phagocytosis/immunology
  • Regeneration/physiology
  • STAT3 Transcription Factor/metabolism
  • Zebrafish/embryology

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