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Myo9b mutations are associated with altered dendritic cell functions and increased susceptibility to autoimmune diabetes onset

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Listed:
  • Jing Zhang

    (Huazhong University of Science and Technology)

  • Yuan Zou

    (Huazhong University of Science and Technology)

  • Longmin Chen

    (Huazhong University of Science and Technology
    Huazhong University of Science and Technology)

  • Fei Sun

    (Huazhong University of Science and Technology)

  • Qianqian Xu

    (Huazhong University of Science and Technology)

  • Qing Zhou

    (Huazhong University of Science and Technology)

  • Yi Wang

    (Huazhong University of Science and Technology)

  • Xi Luo

    (Huazhong University of Science and Technology)

  • Na Wang

    (Huazhong University of Science and Technology)

  • Yang Li

    (Huazhong University of Science and Technology)

  • Shu Zhang

    (Huazhong University of Science and Technology)

  • Fei Xiong

    (Huazhong University of Science and Technology)

  • Ping Yang

    (Huazhong University of Science and Technology)

  • Shiwei Liu

    (Third Hospital of Shanxi Medical University)

  • Tao Yang

    (the First Affiliated Hospital of Nanjing Medical University)

  • Jianping Weng

    (University of Science and Technology of China)

  • Décio L. Eizirik

    (Université Libre de Bruxelles)

  • Jinhua Yan

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

  • Zhiguang Zhou

    (Central South University)

  • Cong-Yi Wang

    (Huazhong University of Science and Technology)

Abstract

The regulation of autoimmunity against pancreatic islet β cells for type 1 diabetes (T1D) onset is still unclear. NOD/ShiLtJ (NOD) mice are prone to the onset of autoimmune diabetes, but its congenic strain, ALR/Lt (ALR), is not. Here we show that dendritic cells (DC) in ALR mice have impaired migratory and T-cell priming capability. Genomic comparative analysis maps a 33-bp deletion in the ALR Myosin IXb (Myo9b) gene when compared with NOD genome; meanwhile, data from knock-in models show that this ALR Myo9b allele impairs phenotypic and functional maturation of DCs, and prevents the development and progression of spontaneous autoimmune diabetes in NOD mice. In parallel, while the ALR 33-bp deletion of Myo9b is not conserved in human, we find a MYO9B R133Q polymorphism associating with increased risk of T1D and enhanced DC function in patients with T1D. Our results thus hint that alterations in Myo9b may contribute to altered DC function and autoimmune diabetes onset.

Suggested Citation

  • Jing Zhang & Yuan Zou & Longmin Chen & Fei Sun & Qianqian Xu & Qing Zhou & Yi Wang & Xi Luo & Na Wang & Yang Li & Shu Zhang & Fei Xiong & Ping Yang & Shiwei Liu & Tao Yang & Jianping Weng & Décio L. E, 2023. "Myo9b mutations are associated with altered dendritic cell functions and increased susceptibility to autoimmune diabetes onset," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-41534-w
    DOI: 10.1038/s41467-023-41534-w
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    Cited by:

    1. Despoina Kyriazi & Lea Voth & Almke Bader & Wiebke Ewert & Juliane Gerlach & Kerstin Elfrink & Peter Franz & Mariana I. Tsap & Bastian Schirmer & Julia Damiano-Guercio & Falk K. Hartmann & Masina Plen, 2024. "An allosteric inhibitor of RhoGAP class-IX myosins suppresses the metastatic features of cancer cells," Nature Communications, Nature, vol. 15(1), pages 1-25, December.

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