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Deubiquitinase Mysm1 regulates macrophage survival and polarization

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Abstract

Macrophages play pivotal roles in innate and adaptive immune response, tissue homeostasis and cancer development. Their development and heterogeneity are tightly controlled by epigenetic program and transcription factors. Deubiquitinase Mysm1 plays crucial roles in regulating stem cell maintenance and immune cell development. Here we show that Mysm1 expression is up regulated during bone marrow macrophage development. Mysm1 deficient cells exhibit accelerating proliferation with more cells going to S phase and higher cyclin D1, cyclin D2 and c-Myc expression. However, compared to WT counterparts, more cell death is also detected in Mysm1 deficient cells no matter M-CSF deprived or not. In LPS-condition medium, Mysm1−/− macrophages show more pro-inflammatory factors IL-1β, TNFα and iNOS production. In addition, much higher expression of surface marker CD86 is detected in Mysm1−/− macrophages. In vivo tumor model data demonstrate that in contrast to WT macrophages promoting tumor growth, Mysm1−/− macrophages inhibit tumor growth, showing the properties of M1 macrophages. Collectively, these data indicate that Mysm1 is essential for macrophage survival and plays an important role in macrophage polarization and might be a target for cell therapy.

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Acknowledgements

The authors sincerely thank Lindsey Jones and Dr. Andrew Woodham for their critical review of this manuscript. This study was financially supported by Beijing Natural Science Foundation (No. 7162142), Program of International Scientific and Technological Cooperation and Exchanges of China (No. 31320103914), National Key Research and Development Program (No. 2016YFC1101303, No. 2017YFA0106100), National Natural Science Foundation of China (No. 81771998, No. 81622027, No. U1601221).

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  1. Xin Zhao, Xiao-Hui Huang and Xiao-Hui Dong contributed equally to this work.

Authors and Affiliations

  1. Department of Neural Engineering and Biological Interdisciplinary Studies, Institute of Military Cognition and Brain Sciences, Academy of Military Medical Sciences, 27 Taiping Road, Haidian District, Beijing, 100850, People’s Republic of China

    Xin Zhao, Xiao-Hui Huang, Xiao-Hui Dong, Yu-Han Wang, Hui-Xin Yang, Yan Wang, Jin Zhou, Changyong Wang & Xiao-Xia Jiang

  2. Department of Urology, First Affiliated Hospital of Jiamusi University, Jiamusi, 154000, Heilongjiang, People’s Republic of China

    Xin Zhao & Shuang Liu

  3. Department of Neurology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, 100020, People’s Republic of China

    Youdi He

  4. Department of Animal Science and Biotechnology, College of Agriculture and Life Science, Chungnam National University, 220 Gung-dong, Yuseong-gu, Daejeon, 305-764, South Korea

    Yu-Han Wang

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  1. Xin Zhao
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Contributions

XXJ and CW conceived and designed the experiments. XZ, XHH, XHD, YHW and HXY performed the experiments. XZ, XHH, XHD, YHW, HXY YW, YH, SL, JZ, XXJ and CW analyzed the data. XXJ and CW contributed reagents, materials and analysis tools. XXJ and CW wrote this manuscript. All authors read and approved the manuscript.

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Correspondence to Changyong Wang or Xiao-Xia Jiang.

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The authors declare no competing interests.

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All animal protocols for the present study are in accordance with the national guidelines for use of animals in scientific research. Additional approval was granted by the Animal Care and Use Committee of Academy of Military Medical Sciences.

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Zhao, X., Huang, XH., Dong, XH. et al. Deubiquitinase Mysm1 regulates macrophage survival and polarization. Mol Biol Rep 45, 2393–2401 (2018). https://doi.org/10.1007/s11033-018-4405-3

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