SENP3 maintains the stability and function of regulatory T cells via BACH2 deSUMOylation

Xiaoyan Yu, Yimin Lao, Xiao Lu Teng, Song Li, Yan Zhou, Feixiang Wang, Xinwei Guo, Siyu Deng, Yuzhou Chang, Xuefeng Wu, Zhiduo Liu, Lei Chen, Li Ming Lu, Jinke Cheng, Bin Li, Bing Su, Jin Jiang, Hua Bing Li, Chuanxin Huang, Jing YiQiang Zou

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11 Scopus citations

Abstract

Regulatory T (Treg) cells are essential for maintaining immune homeostasis and tolerance, but the mechanisms regulating the stability and function of Treg cells have not been fully elucidated. Here we show SUMO-specific protease 3 (SENP3) is a pivotal regulator of Treg cells that functions by controlling the SUMOylation and nuclear localization of BACH2. Treg cell-specific deletion of Senp3 results in T cell activation, autoimmune symptoms and enhanced antitumor T cell responses. SENP3-mediated BACH2 deSUMOylation prevents the nuclear export of BACH2, thereby repressing the genes associated with CD4+ T effector cell differentiation and stabilizing Treg cell-specific gene signatures. Notably, SENP3 accumulation triggered by reactive oxygen species (ROS) is involved in Treg cell-mediated tumor immunosuppression. Our results not only establish the role of SENP3 in the maintenance of Treg cell stability and function via BACH2 deSUMOylation but also clarify the function of SENP3 in the regulation of ROS-induced immune tolerance.

Original languageEnglish (US)
Article number3157
JournalNature communications
Volume9
Issue number1
DOIs
StatePublished - Dec 1 2018

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ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Cite this

Yu, X., Lao, Y., Teng, X. L., Li, S., Zhou, Y., Wang, F., Guo, X., Deng, S., Chang, Y., Wu, X., Liu, Z., Chen, L., Lu, L. M., Cheng, J., Li, B., Su, B., Jiang, J., Li, H. B., Huang, C., ... Zou, Q. (2018). SENP3 maintains the stability and function of regulatory T cells via BACH2 deSUMOylation. Nature communications, 9(1), [3157]. https://doi.org/10.1038/s41467-018-05676-6