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 Yi; Qiang Zou

doi:10.1038/s41467-018-05676-6

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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83 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 language	English (US)
Article number	3157
Journal	Nature communications
Volume	9
Issue number	1
DOIs	https://doi.org/10.1038/s41467-018-05676-6
State	Published - Dec 1 2018

ASJC Scopus subject areas

General Physics and Astronomy
General Chemistry
General Biochemistry, Genetics and Molecular Biology

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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), Article 3157. https://doi.org/10.1038/s41467-018-05676-6

@article{8ad5722767d240729daabb6c98955b01,

title = "SENP3 maintains the stability and function of regulatory T cells via BACH2 deSUMOylation",

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.",

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

note = "Funding Information: This study was supported by grants from the National Natural Science Foundation of China (31230037, 31670896, 31370904, 81671579, 91753141), the Ministry of Science and Technology of China (2013CB910900), the National Key Research and Development Program (2017YFA0104500), the Recruitment Program of Global Experts of China, Shanghai Rising-Star Program (16QA1403300), Shanghai Municipal Commission of Health and Family Planning (20174Y0049, 20174Y0191), Shanghai Jiao Tong University “Program for young teachers” (KJ30214170006) and “Medical and Engineering Cross Research Foundation” (YG2016QN77). Publisher Copyright: {\textcopyright} 2018, The Author(s).",

year = "2018",

month = dec,

day = "1",

doi = "10.1038/s41467-018-05676-6",

language = "English (US)",

volume = "9",

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T1 - SENP3 maintains the stability and function of regulatory T cells via BACH2 deSUMOylation

AU - Yu, Xiaoyan

AU - Lao, Yimin

AU - Teng, Xiao Lu

AU - Li, Song

AU - Zhou, Yan

AU - Wang, Feixiang

AU - Guo, Xinwei

AU - Deng, Siyu

AU - Chang, Yuzhou

AU - Wu, Xuefeng

AU - Liu, Zhiduo

AU - Chen, Lei

AU - Lu, Li Ming

AU - Cheng, Jinke

AU - Li, Bin

AU - Su, Bing

AU - Jiang, Jin

AU - Li, Hua Bing

AU - Huang, Chuanxin

AU - Yi, Jing

AU - Zou, Qiang

N1 - Funding Information: This study was supported by grants from the National Natural Science Foundation of China (31230037, 31670896, 31370904, 81671579, 91753141), the Ministry of Science and Technology of China (2013CB910900), the National Key Research and Development Program (2017YFA0104500), the Recruitment Program of Global Experts of China, Shanghai Rising-Star Program (16QA1403300), Shanghai Municipal Commission of Health and Family Planning (20174Y0049, 20174Y0191), Shanghai Jiao Tong University “Program for young teachers” (KJ30214170006) and “Medical and Engineering Cross Research Foundation” (YG2016QN77). Publisher Copyright: © 2018, The Author(s).

PY - 2018/12/1

Y1 - 2018/12/1

N2 - 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.

AB - 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.

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SN - 2041-1723

VL - 9

JO - Nature communications

JF - Nature communications

IS - 1

M1 - 3157

ER -

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

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