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RNF213 promotes Treg cell differentiation by facilitating K63-linked ubiquitination and nuclear translocation of FOXO1

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  • Xiaofan Yang

    (Guangzhou Medical University)

  • Xiaotong Zhu

    (Southern Medical University)

  • Junli Sheng

    (Guangzhou Medical University)

  • Yuling Fu

    (Guangzhou Medical University)

  • Dingnai Nie

    (Guangzhou Medical University)

  • Xiaolong You

    (Guangzhou Medical University)

  • Yitian Chen

    (Guangzhou Medical University)

  • Xiaodan Yang

    (Guangzhou Medical University)

  • Qiao Ling

    (Guangzhou Medical University)

  • Huili Zhang

    (South China University of Technology)

  • Xiaomin Li

    (Guangzhou Medical University)

  • Shengfeng Hu

    (Guangzhou Medical University
    Southern Medical University)

Abstract

Autoreactive CD4+ T helper cells are critical players that orchestrate the immune response both in multiple sclerosis (MS) and in other neuroinflammatory autoimmune diseases. Ubiquitination is a posttranslational protein modification involved in regulating a variety of cellular processes, including CD4+ T cell differentiation and function. However, only a limited number of E3 ubiquitin ligases have been characterized in terms of their biological functions, particularly in CD4+ T cell differentiation and function. In this study, we found that the RING finger protein 213 (RNF213) specifically promoted regulatory T (Treg) cell differentiation in CD4+ T cells and attenuated autoimmune disease development in an FOXO1-dependent manner. Mechanistically, RNF213 interacts with Forkhead Box Protein O1 (FOXO1) and promotes nuclear translocation of FOXO1 by K63-linked ubiquitination. Notably, RNF213 expression in CD4+ T cells was induced by IFN-β and exerts a crucial role in the therapeutic efficacy of IFN-β for MS. Together, our study findings collectively emphasize the pivotal role of RNF213 in modulating adaptive immune responses. RNF213 holds potential as a promising therapeutic target for addressing disorders associated with Treg cells.

Suggested Citation

  • Xiaofan Yang & Xiaotong Zhu & Junli Sheng & Yuling Fu & Dingnai Nie & Xiaolong You & Yitian Chen & Xiaodan Yang & Qiao Ling & Huili Zhang & Xiaomin Li & Shengfeng Hu, 2024. "RNF213 promotes Treg cell differentiation by facilitating K63-linked ubiquitination and nuclear translocation of FOXO1," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-50392-z
    DOI: 10.1038/s41467-024-50392-z
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    References listed on IDEAS

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    1. Elsje G. Otten & Emma Werner & Ana Crespillo-Casado & Keith B. Boyle & Vimisha Dharamdasani & Claudio Pathe & Balaji Santhanam & Felix Randow, 2021. "Ubiquitylation of lipopolysaccharide by RNF213 during bacterial infection," Nature, Nature, vol. 594(7861), pages 111-116, June.
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