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Article: Mesenchymal stem cell transplantation alleviates experimental Sjögren's syndrome through IFN-β/IL-27 signaling axis

TitleMesenchymal stem cell transplantation alleviates experimental Sjögren's syndrome through IFN-β/IL-27 signaling axis
Authors
KeywordsMesenchymal stem cells
Sjögren's syndrome
IL-27
Issue Date2019
PublisherIvyspring International Publisher. The Journal's web site is located at http://www.thno.org/
Citation
Theranostics, 2019, v. 9 n. 26, p. 8253-8265 How to Cite?
AbstractRationale: Although mesenchymal stem cell (MSC) transplantation has been proved to be an effective therapeutic approach to treat experimental Sjögren's syndrome (SS), the detailed underlying mechanisms remains unknown. IL-27 has diverse influences on the regulation of T cell differentiation and was involved in SS through modulating immune response. Here we aimed to explore whether IL-27-mediated regulation of immune cells was responsible for the beneficial effects of MSC transplantation on SS. Methods: The SS-like symptoms were evaluated in IL-27 deficient and recombinant IL-27-treated NOD mice. The MSCs were infused into NOD mice via the tail vein. The histological features of submandibular glands, saliva flow rate and serum IL-27 were examined. The effects of MSCs on the IL-27 production and Th17/Treg cell in SS patients and mice in vitro and in vivo were determined for the mechanistic study. Results: This study showed that SS patients had decreased IL-27 level and increased ratio of Th17/Treg cells. Consistently, exacerbated SS-like symptoms were observed in IL-27 deficient NOD mice, along with increased ratio of Th17/Treg cells. Importantly, MSC transplantation alleviated SS-like symptoms by elevating the level of IL-27 to restore Th17/Treg balance in NOD mice. Mechanistically, MSC-secreted interferon-β (IFN-β) promote dendritic cells to produce IL-27. Conclusions: Thus, we have revealed a previously unrecognized function of MSC-mediated IL-27 production by DCs in suppressing SS-like syndrome, which provided evidences for clinical application of MSC in patients with SS.
Persistent Identifierhttp://hdl.handle.net/10722/281903
ISSN
2019 Impact Factor: 8.579
2015 SCImago Journal Rankings: 2.702
PubMed Central ID

 

DC FieldValueLanguage
dc.contributor.authorYao, G-
dc.contributor.authorQi, J-
dc.contributor.authorLiang, J-
dc.contributor.authorShi, B-
dc.contributor.authorChen, W-
dc.contributor.authorLi, W-
dc.contributor.authorTang, X-
dc.contributor.authorWang, D-
dc.contributor.authorLu, L-
dc.contributor.authorChen, W-
dc.contributor.authorShi, S-
dc.contributor.authorHou, Y-
dc.contributor.authorSun, L-
dc.date.accessioned2020-04-03T07:23:25Z-
dc.date.available2020-04-03T07:23:25Z-
dc.date.issued2019-
dc.identifier.citationTheranostics, 2019, v. 9 n. 26, p. 8253-8265-
dc.identifier.issn1838-7640-
dc.identifier.urihttp://hdl.handle.net/10722/281903-
dc.description.abstractRationale: Although mesenchymal stem cell (MSC) transplantation has been proved to be an effective therapeutic approach to treat experimental Sjögren's syndrome (SS), the detailed underlying mechanisms remains unknown. IL-27 has diverse influences on the regulation of T cell differentiation and was involved in SS through modulating immune response. Here we aimed to explore whether IL-27-mediated regulation of immune cells was responsible for the beneficial effects of MSC transplantation on SS. Methods: The SS-like symptoms were evaluated in IL-27 deficient and recombinant IL-27-treated NOD mice. The MSCs were infused into NOD mice via the tail vein. The histological features of submandibular glands, saliva flow rate and serum IL-27 were examined. The effects of MSCs on the IL-27 production and Th17/Treg cell in SS patients and mice in vitro and in vivo were determined for the mechanistic study. Results: This study showed that SS patients had decreased IL-27 level and increased ratio of Th17/Treg cells. Consistently, exacerbated SS-like symptoms were observed in IL-27 deficient NOD mice, along with increased ratio of Th17/Treg cells. Importantly, MSC transplantation alleviated SS-like symptoms by elevating the level of IL-27 to restore Th17/Treg balance in NOD mice. Mechanistically, MSC-secreted interferon-β (IFN-β) promote dendritic cells to produce IL-27. Conclusions: Thus, we have revealed a previously unrecognized function of MSC-mediated IL-27 production by DCs in suppressing SS-like syndrome, which provided evidences for clinical application of MSC in patients with SS.-
dc.languageeng-
dc.publisherIvyspring International Publisher. The Journal's web site is located at http://www.thno.org/-
dc.relation.ispartofTheranostics-
dc.rightsTheranostics. Copyright © Ivyspring International Publisher.-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.subjectMesenchymal stem cells-
dc.subjectSjögren's syndrome-
dc.subjectIL-27-
dc.titleMesenchymal stem cell transplantation alleviates experimental Sjögren's syndrome through IFN-β/IL-27 signaling axis-
dc.typeArticle-
dc.identifier.emailLu, L: liweilu@hku.hk-
dc.identifier.authorityLu, L=rp00477-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.7150/thno.37351-
dc.identifier.pmid31754394-
dc.identifier.pmcidPMC6857067-
dc.identifier.scopuseid_2-s2.0-85074326898-
dc.identifier.hkuros309592-
dc.identifier.volume9-
dc.identifier.issue26-
dc.identifier.spage8253-
dc.identifier.epage8265-
dc.publisher.placeAustralia-

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