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Knockout of Stat5 in T cells ameliorates high cholesterol and high fat diet-induced hypercholesterolemia by influencing cholesterol metabolism in the liver

Cellular & Molecular Immunology (2020)Cite this article

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Cholesterol is an essential component of cell barrier formation and signal transduction and is involved in many essential physiologic processes.1 Dysregulation of cholesterol metabolism leads to hypercholesterolemia, which causes multiple diseases, including atherosclerosis.2 The liver plays a central role in cholesterol homeostasis by cholesterol synthesis, as well as clearance, which is regulated by sterol regulatory element-binding proteins (SREBPs) and the reverse cholesterol transport (RCT) process.3,4

STAT5 (STAT5A and STAT5B in mice) is a member of the STAT transcription factor family. In T cells, STAT5 is activated by multiple cytokines and plays a critical role in development and function. Disruption of Stat5a or Stat5b in T cells leads to failure of proliferation in response to IL2. Further research showed that JAK3/STAT5 signaling affects Th1 cell polarization and IFNγ secretion by regulating the expression of T-bet.5,6,7

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References

  1. Ikonen, E. Cellular cholesterol trafficking and compartmentalization. Nat. Rev. Mol. Cell Biol. 9, 125–138 (2008).

    Article  CAS  Google Scholar 

  2. van der Wulp, M. Y., Verkade, H. J. & Groen, A. K. Regulation of cholesterol homeostasis. Mol. Cell Endocrinol. 368, 1–16 (2013).

    Article  Google Scholar 

  3. Horton, J. D., Goldstein, J. L. & Brown, M. S. SREBPs: activators of the complete program of cholesterol and fatty acid synthesis in the liver. J. Clin. Invest. 109, 1125–1131 (2002).

    Article  CAS  Google Scholar 

  4. Wang, S. & Smith, J. D. ABCA1 and nascent HDL biogenesis. Biofactors 40, 547–554 (2014).

    Article  CAS  Google Scholar 

  5. Shi, M. et al. Janus-kinase-3-dependent signals induce chromatin remodeling at the Ifng locus during T helper 1 cell differentiation. Immunity 28, 763–773 (2008).

    Article  CAS  Google Scholar 

  6. Liao, W. et al. Modulation of cytokine receptors by IL-2 broadly regulates differentiation into helper T cell lineages. Nat. Immunol. 12, 551–559 (2011).

    Article  CAS  Google Scholar 

  7. Moriggl, R. et al. Stat5 is required for IL-2-induced cell cycle progression of peripheral T cells. Immunity 10, 249–259 (1999).

    Article  CAS  Google Scholar 

  8. Khera, A. V. & Rader, D. J. Future therapeutic directions in reverse cholesterol transport. Curr. Atheroscler. Rep. 12, 73–81 (2010).

    Article  CAS  Google Scholar 

  9. Owen, D. L. & Farrar, M. A. STAT5 and CD4 (+) T Cell Immunity. F1000Res 6, 32 (2017).

    Article  Google Scholar 

Download references

Acknowledgements

We thank Prof. Bin Li (Shanghai Jiao Tong University College of Basic Medical Sciences), Prof. Jun Qin (Beijing Proteome Research Center) and Prof. Ruijun Tian (Southern University of Science and Technology) for their guidance in the project design. We thank MD. Xianhao Bao provided human blood from the hospital. We thank Yan Gao, Zhen Zhu, Wenxu He, Yuexia Zhang, Yuemei Zhang, and Xuena Zhang for assistance with mouse husbandry and technical assistance. I am really grateful to my parents Haobo Ma and Xiuhong Li for their psychological support. Finally, we thank all of the sacrificed mice. This study was supported by a grant from Nanjing University (Grant Number: 22722001).

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  1. These authors contributed equally: Zhongnan Ma, Na Sheng

Authors and Affiliations

  1. Model Animal Research Center of Nanjing University, 210061, Nanjing, China

    Zhongnan Ma, Na Sheng & Xin-Yuan Fu

  2. Department of Biology, Southern University of Science and Technology, 518055, Shenzhen, China

    Zhongnan Ma, Yixun Su, Tianhao Mu, Jianqiang Xu & Xin-Yuan Fu

  3. West China Hospital, Sichuan University, 610041, Chengdu, Sichuan, China

    Zhongnan Ma, Yi Zhou, Tianhao Mu & Xin-Yuan Fu

  4. Cancer Science Institute of Singapore, Singapore, 117599, Singapore

    Xinyu Liu, Yixun Su, Yi Zhou, Tianhao Mu & Xin-Yuan Fu

  5. Life Sciences Institute, National University of Singapore, Singapore, 117456, Singapore

    Xinyu Liu, Yixun Su, Yi Zhou, Tianhao Mu & Xin-Yuan Fu

  6. The Seventh Affiliated Hospital, Sun Yat-sen University, 518107, Shenzhen, China

    Yixun Su

  7. BGI-Shenzhen, 518083, Shenzhen, China

    Yan Sun

  8. Vascular Surgery Department, Changhai Hospital, 200433, Shanghai, China

    Jiaxuan Feng & Zhiqing Zhao

  9. Navy Medical University, Yangpu District, Shanghai, China

    Jiaxuan Feng & Zhiqing Zhao

Authors
  1. Zhongnan Ma
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  2. Na Sheng
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  9. Jiaxuan Feng
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  10. Zhiqing Zhao
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  11. Xin-Yuan Fu
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Contributions

Z.N.M. and X.Y.F. provided oversight of the study, including experimental design and data interpretation, and wrote the manuscript. Z.N.M. and N.S. contributed equally to this work and performed most of the experiments with assistance from X.Y.L., Y.X.S., Y.Z., Y.S., T.H.M., J.Q.X., contributed reagents and provided scientific insight and discussion. J.X.F. and Z.Q.Z. contributed human samples from the hospital. All authors reviewed and contributed to the manuscript.

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Correspondence to Xin-Yuan Fu.

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The authors declare no competing interests.

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Ma, Z., Sheng, N., Liu, X. et al. Knockout of Stat5 in T cells ameliorates high cholesterol and high fat diet-induced hypercholesterolemia by influencing cholesterol metabolism in the liver. Cell Mol Immunol (2020). https://doi.org/10.1038/s41423-020-0389-8

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  • DOI: https://doi.org/10.1038/s41423-020-0389-8

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