Olfactory ecto-mesenchymal stem cell-derived exosomes ameliorate murine Sjögren’s syndrome by modulating the function of myeloid-derived suppressor cells

被引：0

作者：

Ke Rui

Yue Hong

Qiugang Zhu

Xiaofei Shi

Fan Xiao

Hailong Fu

Qing Yin

Yida Xing

Xinfeng Wu

Xiaodan Kong

Huaxi Xu

Jie Tian

Shengjun Wang

Liwei Lu

机构：

[1] Affiliated Hospital of Jiangsu University,Department of Laboratory Medicine

[2] Jiangsu Key Laboratory of Laboratory Medicine,Department of Immunology

[3] School of Medicine,Department of Rheumatology

[4] Jiangsu University,Department of Pathology and Shenzhen Institute of Research and Innovation

[5] The First Affiliated Hospital and College of Clinical Medicine,Center for Clinical Laboratory

[6] Henan University of Science and Technology,Department of Rheumatology

[7] The University of Hong Kong; Chongqing International Institute for Immunology,undefined

[8] The First Affiliated Hospital of Soochow University,undefined

[9] The Second Affiliated Hospital of Dalian Medical University,undefined

来源：

Cellular & Molecular Immunology | 2021年 / 18卷

关键词：

mesenchymal stem cells; exosomes; MDSCs; Sjögren’s syndrome; autoimmune diseases;

D O I：

暂无

中图分类号：

学科分类号：

摘要：

Sjögren’s syndrome (SS) is a systemic autoimmune disease characterized by progressive inflammation and tissue damage in salivary glands and lacrimal glands. Our previous studies showed that myeloid-derived suppressor cells (MDSCs) exhibited impaired immunosuppressive function during disease progression in patients with SS and mice with experimental Sjögren’s syndrome (ESS), but it remains unclear whether restoring the function of MDSCs can effectively ameliorate the development of ESS. In this study, we found that murine olfactory ecto-mesenchymal stem cell-derived exosomes (OE-MSC-Exos) significantly enhanced the suppressive function of MDSCs by upregulating arginase expression and increasing ROS and NO levels. Moreover, treatment with OE-MSC-Exos via intravenous injection markedly attenuated disease progression and restored MDSC function in ESS mice. Mechanistically, OE-MSC-Exo-secreted IL-6 activated the Jak2/Stat3 pathway in MDSCs. In addition, the abundant S100A4 in OE-MSC-Exos acted as a key factor in mediating the endogenous production of IL-6 by MDSCs via TLR4 signaling, indicating an autocrine pathway of MDSC functional modulation by IL-6. Taken together, our results demonstrated that OE-MSC-Exos possess therapeutic potential to attenuate ESS progression by enhancing the immunosuppressive function of MDSCs, possibly constituting a new strategy for the treatment of Sjögren’s syndrome and other autoimmune diseases.

引用

页码：440 / 451

页数：11

共 68 条

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