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

TitleOlfactory ecto-mesenchymal stem cell-derived exosomes ameliorate murine Sjögren’s syndrome by modulating the function of myeloid-derived suppressor cells
Authors
Keywordsmesenchymal stem cells
exosomes
MDSCs
Sjögren’s syndrome
autoimmune diseases
Issue Date2021
PublisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/cmi/index.html
Citation
Cellular & Molecular Immunology, 2021, v. 18, p. 440-451 How to Cite?
AbstractSjögren’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, OEMSC-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.
Persistent Identifierhttp://hdl.handle.net/10722/304806
ISSN
2023 Impact Factor: 21.8
2023 SCImago Journal Rankings: 4.838
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorRui, K-
dc.contributor.authorHong, Y-
dc.contributor.authorZhu, Q-
dc.contributor.authorShi, X-
dc.contributor.authorXiao, F-
dc.contributor.authorFu, H-
dc.contributor.authorYin, Q-
dc.contributor.authorXing, Y-
dc.contributor.authorWu, X-
dc.contributor.authorKong, X-
dc.contributor.authorXu, H-
dc.contributor.authorTian, J-
dc.contributor.authorWang, S-
dc.contributor.authorLu, L-
dc.date.accessioned2021-10-05T02:35:28Z-
dc.date.available2021-10-05T02:35:28Z-
dc.date.issued2021-
dc.identifier.citationCellular & Molecular Immunology, 2021, v. 18, p. 440-451-
dc.identifier.issn1672-7681-
dc.identifier.urihttp://hdl.handle.net/10722/304806-
dc.description.abstractSjögren’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, OEMSC-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.-
dc.languageeng-
dc.publisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/cmi/index.html-
dc.relation.ispartofCellular & Molecular Immunology-
dc.subjectmesenchymal stem cells-
dc.subjectexosomes-
dc.subjectMDSCs-
dc.subjectSjögren’s syndrome-
dc.subjectautoimmune diseases-
dc.titleOlfactory ecto-mesenchymal stem cell-derived exosomes ameliorate murine Sjögren’s syndrome by modulating the function of myeloid-derived suppressor cells-
dc.typeArticle-
dc.identifier.emailXiao, F: xiaof@hku.hk-
dc.identifier.emailLu, L: liweilu@hku.hk-
dc.identifier.authorityLu, L=rp00477-
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.1038/s41423-020-00587-3-
dc.identifier.pmid33408339-
dc.identifier.pmcidPMC8027615-
dc.identifier.scopuseid_2-s2.0-85098786611-
dc.identifier.hkuros326253-
dc.identifier.volume18-
dc.identifier.spage440-
dc.identifier.epage451-
dc.identifier.isiWOS:000605527500005-
dc.publisher.placeChina-

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