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

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. Eizirik, Jinhua Yan (), Zhiguang Zhou () and Cong-Yi Wang ()
Additional contact information
Jing Zhang: Huazhong University of Science and Technology
Yuan Zou: Huazhong University of Science and Technology
Longmin Chen: 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

Nature Communications, 2023, vol. 14, issue 1, 1-17

Abstract: 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.

Date: 2023
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DOI: 10.1038/s41467-023-41534-w

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