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

Anthony J. Covarrubias, Halil Ibrahim Aksoylar, Jiujiu Yu, Nathaniel W. Snyder, Andrew J. Worth, Shankar S. Iyer, Jiawei Wang, Issam Ben-Sahra, Vanessa Byles, Tiffany Polynne-Stapornkul, Erika C. Espinosa, Dudley Lamming, Brendan D. Manning, Yijing Zhang, Ian A. Blair, Tiffany Horng*

*Corresponding author for this work

Research output: Contribution to journalArticle

140 Scopus citations

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.

Original languageEnglish (US)
Article numbere11612
JournaleLife
Volume5
Issue numberFEBRUARY2016
DOIs
StatePublished - Feb 19 2016

ASJC Scopus subject areas

  • Neuroscience(all)
  • Immunology and Microbiology(all)
  • Biochemistry, Genetics and Molecular Biology(all)

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    Covarrubias, A. J., Aksoylar, H. I., Yu, J., Snyder, N. W., Worth, A. J., Iyer, S. S., Wang, J., Ben-Sahra, I., Byles, V., Polynne-Stapornkul, T., Espinosa, E. C., Lamming, D., Manning, B. D., Zhang, Y., Blair, I. A., & Horng, T. (2016). Akt-mTORC1 signaling regulates Acly to integrate metabolic input to control of macrophage activation. eLife, 5(FEBRUARY2016), [e11612]. https://doi.org/10.7554/eLife.11612