Macrophages Switch Their Phenotype by Regulating Maf Expression during Different Phases of Inflammation

J Immunol. 2018 Jul 15;201(2):635-651. doi: 10.4049/jimmunol.1800040. Epub 2018 Jun 15.


Macrophages manifest distinct phenotype according to the organs in which they reside. In addition, they flexibly switch their character in adaptation to the changing environment. However, the molecular basis that explains the conversion of the macrophage phenotype has so far been unexplored. We find that CD169+ macrophages change their phenotype by regulating the level of a transcription factor Maf both in vitro and in vivo in C57BL/6J mice. When CD169+ macrophages were exposed to bacterial components, they expressed an array of acute inflammatory response genes in Maf-dependent manner and simultaneously start to downregulate Maf. This Maf suppression is dependent on accelerated degradation through proteasome pathway and microRNA-mediated silencing. The downregulation of Maf unlocks the NF-E2-related factor 2-dominant, cytoprotective/antioxidative program in the same macrophages. The present study provides new insights into the previously unanswered question of how macrophages initiate proinflammatory responses while retaining their capacity to repair injured tissues during inflammation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation
  • Cells, Cultured
  • Female
  • Gene Expression Regulation
  • Inflammation / immunology*
  • Lipopolysaccharides / immunology
  • Macrophages / physiology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • MicroRNAs / genetics
  • NF-E2-Related Factor 2 / metabolism
  • Phenotype
  • Proteasome Endopeptidase Complex / metabolism*
  • Proteolysis
  • Proto-Oncogene Proteins c-maf / genetics
  • Proto-Oncogene Proteins c-maf / metabolism*
  • Sialic Acid Binding Ig-like Lectin 1 / metabolism


  • Lipopolysaccharides
  • Maf protein, mouse
  • MicroRNAs
  • NF-E2-Related Factor 2
  • NFE2L2 protein, human
  • Proto-Oncogene Proteins c-maf
  • Sialic Acid Binding Ig-like Lectin 1
  • Proteasome Endopeptidase Complex