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Theranostics 2023; 13(11):3509-3523. doi:10.7150/thno.86307 This issue Cite

Research Paper

RNF157 attenuates CD4+ T cell-mediated autoimmune response by promoting HDAC1 ubiquitination and degradation

Peng Wang1#, Jingjing Zhao2,3#, Yunke Tan1, Junli Sheng4, Shitong He4, Yitian Chen4, Dingnai Nie4, Xiaolong You4, Jinmei Luo5✉, Yanling Zhang6✉, Shengfeng Hu4,7✉

1. Department of Emergency Medicine, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.
2. Department of Biotherapy, Sun Yat-sen University Cancer Center, Guangzhou, China.
3. State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China.
4. The Second Affiliated Hospital, The State Key Laboratory of Respiratory Disease, Guangdong Provincial Key Laboratory of Allergy & Clinical Immunology, Guangzhou Medical University, Guangzhou, China.
5. Department of Internal Medicine, Medical Intensive Care Unit and Division of Respiratory Diseases, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
6. Experimental Center of Teaching and Scientific Research, School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou, China.
7. Department of Rheumatology and Clinical Immunology, Zhujiang Hospital, Southern Medical University, Guangzhou, China.
# These authors contributed equally to this work.

✉ Corresponding authors: Shengfeng Hu, M.D., Ph.D. E-mail: hushengfengedu.cn; Yanliang Zhang, M.D., Ph.D. E-mail: drzyledu.cn; Jinmei Luo, M.D., Ph.D. E-mail: luojm3sysu.edu.cn

Citation:
Wang P, Zhao J, Tan Y, Sheng J, He S, Chen Y, Nie D, You X, Luo J, Zhang Y, Hu S. RNF157 attenuates CD4+ T cell-mediated autoimmune response by promoting HDAC1 ubiquitination and degradation. Theranostics 2023; 13(11):3509-3523. doi:10.7150/thno.86307. https://www.thno.org/v13p3509.htm
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Abstract

Graphic abstract

Background: CD4+ T cells play an important role in body development and homeostasis. Quantitative and functional changes in CD4+ T cells result in abnormal immune responses, which lead to inflammation, cancer, or autoimmune diseases, such as multiple sclerosis (MS). Ubiquitination plays an essential role in the differentiation and functioning of CD4+ T cells. However, the function of several E3 ubiquitin ligases in CD4+ T cell differentiation and T cell-mediated pathological diseases remains unclear.

Methods: RNA sequencing data were analyzed to identify the E3 ubiquitin ligases that participate in the pathogenesis of MS. Furthermore, conditional knockout mice were generated. Specifically, flow cytometry, qPCR, western blot, CO-IP and cell transfer adoptive experiments were performed.

Results: In this study, we identified The RING finger 157 (RNF157) as a vital regulator of CD4+ T cell differentiation; it promoted Th1 differentiation but attenuated Th17 differentiation and CCR4 and CXCR3 expressions in CD4+ T cells, thereby limiting experimental autoimmune encephalomyelitis development. Mechanistically, RNF157 in CD4+ T cells targeted HDAC1 for K48-linked ubiquitination and degradation. Notably, RNF157 expression was significantly decreased and showed a significant negative correlation with RORγt expression in patients with MS.

Conclusions: Our study highlights the critical role of RNF157 in regulating CD4+ T cell functions in autoimmune diseases and suggests RNF157 as a potential target in adaptive immune responses against MS and other autoimmune disorders.

Keywords: CD4+ T cells, RNF157, HDAC1, Multiple sclerosis, Ubiquitination

Citation styles

APA
Wang, P., Zhao, J., Tan, Y., Sheng, J., He, S., Chen, Y., Nie, D., You, X., Luo, J., Zhang, Y., Hu, S. (2023). RNF157 attenuates CD4+ T cell-mediated autoimmune response by promoting HDAC1 ubiquitination and degradation. Theranostics, 13(11), 3509-3523. https://doi.org/10.7150/thno.86307.

ACS
Wang, P.; Zhao, J.; Tan, Y.; Sheng, J.; He, S.; Chen, Y.; Nie, D.; You, X.; Luo, J.; Zhang, Y.; Hu, S. RNF157 attenuates CD4+ T cell-mediated autoimmune response by promoting HDAC1 ubiquitination and degradation. Theranostics 2023, 13 (11), 3509-3523. DOI: 10.7150/thno.86307.

NLM
Wang P, Zhao J, Tan Y, Sheng J, He S, Chen Y, Nie D, You X, Luo J, Zhang Y, Hu S. RNF157 attenuates CD4+ T cell-mediated autoimmune response by promoting HDAC1 ubiquitination and degradation. Theranostics 2023; 13(11):3509-3523. doi:10.7150/thno.86307. https://www.thno.org/v13p3509.htm

CSE
Wang P, Zhao J, Tan Y, Sheng J, He S, Chen Y, Nie D, You X, Luo J, Zhang Y, Hu S. 2023. RNF157 attenuates CD4+ T cell-mediated autoimmune response by promoting HDAC1 ubiquitination and degradation. Theranostics. 13(11):3509-3523.

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