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Extracellular vesicle–encapsulated miR-10a-5p derived from MDSCs restrains germinal center B cells in experimental Sjögren’s syndrome

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Abstract

Primary Sjögren’s syndrome (pSS) is a progressive systemic autoimmune disease characterized by chronic inflammation of the exocrine glands, resulting in damage to the salivary and lacrimal glands. Our group and other researchers have reported that myeloid-derived suppressor cell-derived extracellular vesicles (MDSC-EVs) could attenuate the progression of autoimmune disease by impairing T-cell function. However, the effect of MDSC-EVs on B-cell function and the underlying mechanism remains largely unknown. In this study, we found that MDSC-EVs significantly attenuated the progression of experimental Sjögren’s syndrome (ESS). Moreover, treatment with MDSC-EVs via intravenous injection markedly reduced the percentage of germinal center (GC) B cells in ESS mice. In vitro, MDSC-EVs could directly suppress the generation of GC B cells and the expression of B cell lymphoma 6 (Bcl-6) in B cells under GC B-cell-polarizing conditions. Mechanistically, miR-10a-5p carried by MDSC-EVs regulated the differentiation of GC B cells by targeting Bcl-6, and inhibition of miR-10a-5p in MDSC-EVs significantly reversed the effect of MDSC-EVs involved in alleviating the development of ESS. Taken together, our findings demonstrated that miR-10a-5p carried by MDSC-EVs inhibited the generation of B cells by targeting Bcl-6 and eventually alleviated the progression of ESS, which may provide novel therapeutic targets for the treatment of pSS.

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Data availability statement

The data that support the findings of this study are included within the manuscript.

Abbreviations

SS :

Sjögren’s syndrome

SGs :

salivary glands

GCs :

germinal centers

DC :

dendritic cell

MZ :

marginal zone

MDSCs :

myeloid-derived suppressor cells

EVs :

extracellular vesicles

Treg :

regulatory T cell

miRNAs :

microRNAs

Bcl-6 :

B cell lymphoma 6

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Acknowledgements

We thank Dr. Dingqi Feng for performing flow cytometric analysis.

Funding

This work was supported by the Jiangsu Provincial Medical Key Discipline Cultivation Unit (Grant No. JSDW202241) and Jiangsu Province “333” Project (Grant No. BRA2017128).

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Authors and Affiliations

  1. Department of Laboratory Medicine, The Affiliated People’s Hospital, Jiangsu University, Zhenjiang, China

    Huimin Zhou, Zhenwei Mao, Yue Zhang, Jun Yang & Shengjun Wang

  2. Department of Immunology, Jiangsu Key Laboratory of Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, China

    Huimin Zhou, Qiugang Zhu, Min Li, Jie Ma, Jie Tian & Shengjun Wang

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  1. Huimin Zhou
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Contributions

HZ and QZ performed the experiments, analyzed the data, and wrote the manuscript; ML, YZ, JY, and JT analyzed the data; ZM and JM discussed and revised the manuscript; and SW designed the study and revised the manuscript. All authors read and approved the final manuscript.

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Correspondence to Shengjun Wang.

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Zhou, H., Zhu, Q., Mao, Z. et al. Extracellular vesicle–encapsulated miR-10a-5p derived from MDSCs restrains germinal center B cells in experimental Sjögren’s syndrome. Immunol Res 71, 760–770 (2023). https://doi.org/10.1007/s12026-023-09390-4

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