Akt-mTORC1 signaling regulates Acly to integrate metabolic input to control of macrophage activation

Elife. 2016 Feb 19;5:e11612. doi: 10.7554/eLife.11612.


Macrophage activation/polarization to distinct functional states is critically supported by metabolic shifts. How polarizing signals coordinate metabolic and functional reprogramming, and the potential implications for control of macrophage activation, remains poorly understood. Here we show that IL-4 signaling co-opts the Akt-mTORC1 pathway to regulate Acly, a key enzyme in Ac-CoA synthesis, leading to increased histone acetylation and M2 gene induction. Only a subset of M2 genes is controlled in this way, including those regulating cellular proliferation and chemokine production. Moreover, metabolic signals impinge on the Akt-mTORC1 axis for such control of M2 activation. We propose that Akt-mTORC1 signaling calibrates metabolic state to energetically demanding aspects of M2 activation, which may define a new role for metabolism in supporting macrophage activation.

Keywords: acly; akt; cell biology; immunology; immunometabolism; mTORC1; macrophage activation; macrophage metabolism; mouse.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • ATP Citrate (pro-S)-Lyase / metabolism*
  • Acetylation
  • Animals
  • Cell Proliferation
  • Chemokines / metabolism
  • Gene Expression Regulation
  • Histones / metabolism
  • Interleukin-4 / metabolism
  • Macrophage Activation*
  • Macrophages / metabolism*
  • Macrophages / physiology
  • Mechanistic Target of Rapamycin Complex 1
  • Mice, Inbred C57BL
  • Multiprotein Complexes / metabolism*
  • Protein Processing, Post-Translational
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Signal Transduction*
  • TOR Serine-Threonine Kinases / metabolism*


  • Chemokines
  • Histones
  • IL4 protein, human
  • Multiprotein Complexes
  • Interleukin-4
  • ATP Citrate (pro-S)-Lyase
  • Mechanistic Target of Rapamycin Complex 1
  • Proto-Oncogene Proteins c-akt
  • TOR Serine-Threonine Kinases