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

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

Author information

1
Department of Genetics and Complex Diseases, Harvard T.H. Chan School of Public Health, Boston, United States.
2
Center of Excellence in Environmental Toxicology, University of Pennsylvania, Philadelphia, United States.
3
A.J. Drexel Autism Institute, Drexel University, Philadelphia, United States.
4
Department of Medicine, Brigham and Women's Hospital, Boston, United States.
5
Institute for Plant Physiology and Ecology, Shanghai Institute for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
6
Department of Medicine, University of Wisconsin-Madison, Madison, United States.

Abstract

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

PMID:
26894960
PMCID:
PMC4769166
DOI:
10.7554/eLife.11612
[Indexed for MEDLINE]
Free PMC Article

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