4.6 Article

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

Journal

JOURNAL OF IMMUNOLOGY
Volume 200, Issue 3, Pages 1169-1187

Publisher

AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.1701247

Keywords

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Categories

Funding

  1. Medical Research Council Program Grant [MR/J010766/1]
  2. UK Regenerative Medicine Platform (UKRMP) Hub Grant [MR/K026666/1]
  3. Centre for the Computational and Chemical Biology of the Niche
  4. UKRMP Hub Grant [MR/L012766/1]
  5. Medical Research Council
  6. Leverhulme Trust
  7. AMMF
  8. Welcome Trust
  9. Bloodwise research grant
  10. Computational and Chemical Biology of the Stem Cell Niche
  11. BBSRC [BBS/E/D/20221657, BBS/E/D/10002071] Funding Source: UKRI
  12. MRC [G0401643, MR/J003611/1, MC_PC_15049, G0801924, MR/J010766/1, G0901697, G1000868, G0900550, G0600033, MR/L012766/1, G0800682, MR/K026666/1] Funding Source: UKRI
  13. Wellcome Trust [100104/Z/12/Z] Funding Source: Wellcome Trust
  14. Biotechnology and Biological Sciences Research Council [BBS/E/D/10002071, BBS/E/D/20221657] Funding Source: researchfish
  15. Medical Research Council [G0401643, G0901697, G1000868, MC_PC_15049, MR/J003611/1, G0801924, MR/K026666/1, MR/L012766/1, G0600033, G0900550, G0800682, MR/J010766/1] Funding Source: researchfish
  16. Wellcome Trust [100104/Z/12/Z] Funding Source: researchfish

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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.

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