Akt-mTORC1 signaling regulates Acly to integrate metabolic input to control of macrophage activation.
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.
['Covarrubias|Anthony J|AJ|', 'Aksoylar|Halil Ibrahim|HI|http://orcid.org/0000-0002-0527-6124', 'Yu|Jiujiu|J|', 'Snyder|Nathaniel W|NW|', 'Worth|Andrew J|AJ|', 'Iyer|Shankar S|SS|', 'Wang|Jiawei|J|', 'Ben-Sahra|Issam|I|', 'Byles|Vanessa|V|', 'Polynne-Stapornkul|Tiffany|T|', 'Espinosa|Erika C|EC|', 'Lamming|Dudley|D|', 'Manning|Brendan D|BD|', 'Zhang|Yijing|Y|', 'Blair|Ian A|IA|', 'Horng|Tiffany|T|']
D001275:ATP Citrate (pro-S)-Lyase D000107:Acetylation D000818:Animals D049109:Cell Proliferation D018925:Chemokines D005786:Gene Expression Regulation D006657:Histones D015847:Interleukin-4 D008262:Macrophage Activation D008264:Macrophages D000076222:Mechanistic Target of Rapamycin Complex 1 D008810:Mice, Inbred C57BL D046912:Multiprotein Complexes D011499:Protein Processing, Post-Translational D051057:Proto-Oncogene Proteins c-akt D015398:Signal Transduction D058570:TOR Serine-Threonine Kinases
acly macrophage activation akt cell biology immunology immunometabolism mTORC1 macrophage metabolism mouse