期刊
CELLULAR & MOLECULAR IMMUNOLOGY
卷 18, 期 2, 页码 440-451出版社
CHIN SOCIETY IMMUNOLOGY
DOI: 10.1038/s41423-020-00587-3
关键词
mesenchymal stem cells; exosomes; MDSCs; Sjogren's syndrome; autoimmune diseases
类别
资金
- National Natural Science Foundation of China [81701612, 81971542, 81702080, 82071817]
- Natural Science Foundation of Jiangsu [BK20170563]
- Chongqing International Institute for Immunology [2020YJC10]
- Summit of the Six Top Talents Program of Jiangsu Province [2017-YY-006]
- Youth Science and Technology Talent Promotion Project of Jiangsu and Hong Kong Croucher Foundation [260960116]
The study demonstrated that murine olfactory ecto-mesenchymal stem cell-derived exosomes can effectively attenuate the progression of experimental Sjogren's syndrome (ESS) by enhancing the immunosuppressive function of myeloid-derived suppressor cells (MDSCs). These exosomes activated the Jak2/Stat3 pathway in MDSCs through IL-6 secretion, and promoted the endogenous production of IL-6 via TLR4 signaling, indicating a potential autocrine pathway for MDSC functional modulation.
Sjogren'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 Sjogren'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 Sjogren's syndrome and other autoimmune diseases.
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