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Olfactory ecto-mesenchymal stem cell-derived exosomes ameliorate murine Sjögren’s syndrome by modulating the function of myeloid-derived suppressor cells
by
Wu, Xinfeng
, Kong Xiaodan
, Shi, Xiaofei
, Yin Qing
, Lu, Liwei
, Xu Huaxi
, Ke, Rui
, Fan, Xiao
, Zhu Qiugang
, Fu Hailong
, Hong, Yue
, Xing Yida
, Tian Jie
, Wang, Shengjun
in
Arginase
/ Autocrine signalling
/ Autoimmune diseases
/ Disease
/ Disease progression
/ Exosomes
/ Inflammation
/ Interleukin 6
/ Intravenous administration
/ Janus kinase 2
/ Lacrimal gland and Nasolacrimal duct
/ Mesenchymal stem cells
/ S100A4 protein
/ Salivary gland
/ Sjogren's syndrome
/ Stat3 protein
/ Stem cells
/ Suppressor cells
/ TLR4 protein
/ Toll-like receptors
2021
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Olfactory ecto-mesenchymal stem cell-derived exosomes ameliorate murine Sjögren’s syndrome by modulating the function of myeloid-derived suppressor cells
by
Wu, Xinfeng
, Kong Xiaodan
, Shi, Xiaofei
, Yin Qing
, Lu, Liwei
, Xu Huaxi
, Ke, Rui
, Fan, Xiao
, Zhu Qiugang
, Fu Hailong
, Hong, Yue
, Xing Yida
, Tian Jie
, Wang, Shengjun
in
Arginase
/ Autocrine signalling
/ Autoimmune diseases
/ Disease
/ Disease progression
/ Exosomes
/ Inflammation
/ Interleukin 6
/ Intravenous administration
/ Janus kinase 2
/ Lacrimal gland and Nasolacrimal duct
/ Mesenchymal stem cells
/ S100A4 protein
/ Salivary gland
/ Sjogren's syndrome
/ Stat3 protein
/ Stem cells
/ Suppressor cells
/ TLR4 protein
/ Toll-like receptors
2021
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Olfactory ecto-mesenchymal stem cell-derived exosomes ameliorate murine Sjögren’s syndrome by modulating the function of myeloid-derived suppressor cells
by
Wu, Xinfeng
, Kong Xiaodan
, Shi, Xiaofei
, Yin Qing
, Lu, Liwei
, Xu Huaxi
, Ke, Rui
, Fan, Xiao
, Zhu Qiugang
, Fu Hailong
, Hong, Yue
, Xing Yida
, Tian Jie
, Wang, Shengjun
in
Arginase
/ Autocrine signalling
/ Autoimmune diseases
/ Disease
/ Disease progression
/ Exosomes
/ Inflammation
/ Interleukin 6
/ Intravenous administration
/ Janus kinase 2
/ Lacrimal gland and Nasolacrimal duct
/ Mesenchymal stem cells
/ S100A4 protein
/ Salivary gland
/ Sjogren's syndrome
/ Stat3 protein
/ Stem cells
/ Suppressor cells
/ TLR4 protein
/ Toll-like receptors
2021
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Olfactory ecto-mesenchymal stem cell-derived exosomes ameliorate murine Sjögren’s syndrome by modulating the function of myeloid-derived suppressor cells
Journal Article
Olfactory ecto-mesenchymal stem cell-derived exosomes ameliorate murine Sjögren’s syndrome by modulating the function of myeloid-derived suppressor cells
2021
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Overview
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.
Publisher
Nature Publishing Group
Subject
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