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Requirement for POH1 in differentiation and maintenance of regulatory T cells

Cell Death & Differentiationvolume 26pages751762 (2019) | Download Citation


Foxp3-expressing regulatory T (Treg) cells are essential for averting autoimmune diseases and maintaining immune homeostasis. However, the molecular mechanisms underlying the development and maintenance of Treg cells are still unclear. Here, we found that T cell-specific deletion of the gene encoding the deubiquitinase POH1 compromised the development of mature T cells, especially CD4+Foxp3+ Treg cells. Moreover, POH1 deficiency significantly attenuated the transition of CD25+ Treg cell precursors into Foxp3+ Treg cells accompanied by downregulation of interleukin 2 (IL-2)-STAT5 signaling. Deletion of POH1 in generated CD4+Foxp3+ Treg cells led to an early onset of fetal autoimmune disorders and a decrease in the pool size of peripheral Treg cells in mice, which were mostly due to decreased expansion of these cells. Thus, these results revealed that POH1 has a pivotal role in the development and maintenance of CD4+Foxp3+ Treg cells and contributes to immune tolerance.

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This work was supported by grants from National Natural Science Foundation of China (31770976, 81572293, and 81402348), the State Key Laboratory of Oncogenes and Related Genes (91–1705), the Shanghai Rising-Star Program (17QA1403700).

Author contributions

YL and YZL designed research; YL, LZ, BSW, ZJY, GQX, AHM, MT, TTJ, LW, and XLX performed research; YL, LZ, and YZL analyzed data; and YL, LZ, and YZL wrote the paper.

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Author notes

  1. These authors contributed equally: Yun Liu, Li Zhang.


  1. State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200032, China

    • Yun Liu
    • , Li Zhang
    • , Boshi Wang
    • , Zhaojuan Yang
    • , Guiqin Xu
    • , Aihui Ma
    • , Ming Tang
    • , Tiantian Jing
    • , Lin Wu
    • , Xiaoli Xu
    •  & Yongzhong Liu


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The authors declare that they have no conflict of interest.

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Correspondence to Yongzhong Liu.

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