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Requirement for POH1 in differentiation and maintenance of regulatory T cells

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

Abstract

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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Edited by M. Piacentini.

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Acknowledgements

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.

Affiliations

  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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DOI

https://doi.org/10.1038/s41418-018-0162-z