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N-acetyltransferase 10 is implicated in the pathogenesis of cycling T cell-mediated autoimmune and inflammatory disorders in mice

Author

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  • Wen-ping Li

    (the Third Affiliated Hospital of Sun Yat-sen University)

  • Xin-tao Mao

    (the Third Affiliated Hospital of Sun Yat-sen University)

  • Jia-huan Xie

    (Zhejiang University)

  • Jie-yu Li

    (the Third Affiliated Hospital of Sun Yat-sen University)

  • Bao-qin Liu

    (Zhejiang University)

  • Le-xi Wu

    (College of Medicine Zhejiang University)

  • Bing Yang

    (Zhejiang University)

  • Yi-yuan Li

    (Southeast University)

  • Jin Jin

    (the Third Affiliated Hospital of Sun Yat-sen University
    Zhejiang University
    College of Medicine Zhejiang University)

Abstract

T cell expansion has a crucial function in both autoimmune and chronic inflammatory diseases, with cycling T cells contributing to the pathogenesis of autoimmune diseases by causing uncontrolled immune responses and tissue damage. Yet the regulatory mechanisms governing T cell expansion remain incompletely understood. Here we show that the enzyme N-acetyltransferase 10 (NAT10) regulates T cell activation and proliferation upon antigen stimulation. T cell-specific NAT10 deficiency in mice reduces the number of mature T cells in peripheral lymphoid organs. Mechanistically, NAT10 acetylates RACK1 at K185, preventing subsequent RACK1 K48-linked ubiquitination and degradation. The increased RACK1 stability alters ribosome formation and cellular metabolism, leading to enhanced supply of energy and biosynthetic precursors and, eventually, T cell proliferation. Our findings thus highlight the essential function of NAT10 in T cell self-renewal and metabolism and elucidate NAT10 mode of action for the potential development of novel therapies for immune-related disorders.

Suggested Citation

  • Wen-ping Li & Xin-tao Mao & Jia-huan Xie & Jie-yu Li & Bao-qin Liu & Le-xi Wu & Bing Yang & Yi-yuan Li & Jin Jin, 2024. "N-acetyltransferase 10 is implicated in the pathogenesis of cycling T cell-mediated autoimmune and inflammatory disorders in mice," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-53350-x
    DOI: 10.1038/s41467-024-53350-x
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    1. Wei-Chun Chou & Zengli Guo & Hao Guo & Liang Chen & Ge Zhang & Kaixin Liang & Ling Xie & Xianming Tan & Sara A. Gibson & Elena Rampanelli & Yan Wang & Stephanie A. Montgomery & W. June Brickey & Meng , 2021. "AIM2 in regulatory T cells restrains autoimmune diseases," Nature, Nature, vol. 591(7849), pages 300-305, March.
    2. Wei-Chun Chou & Zengli Guo & Hao Guo & Liang Chen & Ge Zhang & Kaixin Liang & Ling Xie & Xianming Tan & Sara A. Gibson & Elena Rampanelli & Yan Wang & Stephanie A. Montgomery & W. June Brickey & Meng , 2021. "Author Correction: AIM2 in regulatory T cells restrains autoimmune diseases," Nature, Nature, vol. 592(7856), pages 29-29, April.
    3. Xue Jiang & Yu Cheng & Yuzhang Zhu & Caoling Xu & Qiaodan Li & Xuemei Xing & Wenqing Li & Jiaqi Zou & Lan Meng & Muhammad Azhar & Yuzhu Cao & Xianhong Tong & Weibing Qin & Xiaoli Zhu & Jianqiang Bao, 2023. "Maternal NAT10 orchestrates oocyte meiotic cell-cycle progression and maturation in mice," Nature Communications, Nature, vol. 14(1), pages 1-23, December.
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