Multi-omics analysis identifies FoxO1 as a regulator of macrophage function through metabolic reprogramming.

Kai Yan, Tian-Tian Da, Zhen-Hua Bian, Yi He, Meng-Chu Liu, Qing-Zhi Liu, Jie Long, Liang Li, Cai-Yue Gao, Shu-Han Yang, Zhi-Bin Zhao, Zhe-Xiong Lian

Cell death & disease 2020 Sep 24

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Macrophages are plastic cells that can switch among different states according to bioenergetic or biosynthetic requirements. Our previous work demonstrated that the transcription factor Forkhead Box Protein 1 (FoxO1) plays a pivotal role in regulating the function of macrophages, but the underlying mechanisms are still unclear. Here we identify FoxO1 as a regulator of macrophage function through metabolic reprogramming. Transcriptomic and proteomic analyses showed that the deficiency of FoxO1 results in an alternatively activated (M2) phenotype of macrophages, with lower expression of inflammatory response- and migration-associated genes. Using the high content screening and analysis technology, we found that deletion of FoxO1 in macrophages slows their migration rate and impairs their function to limit tumor cell growth in vitro. Next, we demonstrated that glycolysis is inhibited in FoxO1-deficient macrophages, which leads to the observed functional changes and the reduced tumor suppression capability. This prospective study shows that FoxO1 serves as a bridge between metabolism and macrophage function.

Citation

Kai Yan, Tian-Tian Da, Zhen-Hua Bian, Yi He, Meng-Chu Liu, Qing-Zhi Liu, Jie Long, Liang Li, Cai-Yue Gao, Shu-Han Yang, Zhi-Bin Zhao, Zhe-Xiong Lian. Multi-omics analysis identifies FoxO1 as a regulator of macrophage function through metabolic reprogramming. Cell death & disease. 2020 Sep 24;11(9):800