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Article: Mesenchymal stem cell transplantation ameliorates Sjögren’s syndrome via suppressing IL-12 production by dendritic cells

TitleMesenchymal stem cell transplantation ameliorates Sjögren’s syndrome via suppressing IL-12 production by dendritic cells
Authors
KeywordsMesenchymal stem cells
Sjögren’s syndrome
Interleukin-12
Issue Date2018
PublisherBioMed Central Ltd. The Journal's web site is located at http://www.stemcellres.com
Citation
Stem Cell Research & Therapy, 2018, v. 9, p. article no. 308 How to Cite?
AbstractBackground: Mesenchymal stem cells (MSCs) have been demonstrated to be effective in treating autoimmune diseases including Sjögren’s syndrome (SS). We aim to compare the effects of MSC transplantation (MSCT) and the role of serum interleukin-12 (IL-12) in SS. Methods: IL-12 levels were measured by ELISA. IL-12 mRNA transcripts in dendritic cells (DCs) were determined by RT-PCR. After co-culturing with MSCs, IL-12 mRNA transcripts in mouse and human DCs were detected. Non-obese diabetic (NOD) mice received MSCT, recombinant IL-12, or anti-IL-12 mAb treatment, respectively. Then, salivary flow rates, histopathology of salivary glands, and splenic lymphocyte subsets were examined in these mice. Results: IL-12 levels in the serum were significantly increased in SS patients and positively correlated with the EULAR 2010 Sjögren’s syndrome disease activity index. DCs from SS patients produced more IL-12 than those from the control. Likewise, IL-12 treatment in NOD mice significantly decreased salivary flow rates and promoted lymphocyte infiltration in salivary glands. IL-12 antibodies downregulated Th1, Th17, and Tfh cell. MSCT enhanced salivary flow rates and decreased lymphocyte infiltrations in salivary glands of NOD mice. MSCT downregulated Th17 and Tfh cells but upregulated regulatory T cells. MSCT reduced IL-12 productions in both SS patients and mice. Conclusion: Our results indicate that MSCs ameliorate SS possibly via suppressing IL-12 production in DCs and that IL-12 could be a potential therapeutic target of SS. Trial registration: NTC00953485. Registered June 2009.
Persistent Identifierhttp://hdl.handle.net/10722/279208
ISSN
2017 Impact Factor: 4.963
2015 SCImago Journal Rankings: 1.405
PubMed Central ID

 

DC FieldValueLanguage
dc.contributor.authorShi, B-
dc.contributor.authorQi, J-
dc.contributor.authorYao, G-
dc.contributor.authorFeng, R-
dc.contributor.authorZhang, Z-
dc.contributor.authorWang, D-
dc.contributor.authorChen, C-
dc.contributor.authorTang, X-
dc.contributor.authorLu, L-
dc.contributor.authorChen, W-
dc.contributor.authorSun, L-
dc.date.accessioned2019-10-21T02:21:35Z-
dc.date.available2019-10-21T02:21:35Z-
dc.date.issued2018-
dc.identifier.citationStem Cell Research & Therapy, 2018, v. 9, p. article no. 308-
dc.identifier.issn1757-6512-
dc.identifier.urihttp://hdl.handle.net/10722/279208-
dc.description.abstractBackground: Mesenchymal stem cells (MSCs) have been demonstrated to be effective in treating autoimmune diseases including Sjögren’s syndrome (SS). We aim to compare the effects of MSC transplantation (MSCT) and the role of serum interleukin-12 (IL-12) in SS. Methods: IL-12 levels were measured by ELISA. IL-12 mRNA transcripts in dendritic cells (DCs) were determined by RT-PCR. After co-culturing with MSCs, IL-12 mRNA transcripts in mouse and human DCs were detected. Non-obese diabetic (NOD) mice received MSCT, recombinant IL-12, or anti-IL-12 mAb treatment, respectively. Then, salivary flow rates, histopathology of salivary glands, and splenic lymphocyte subsets were examined in these mice. Results: IL-12 levels in the serum were significantly increased in SS patients and positively correlated with the EULAR 2010 Sjögren’s syndrome disease activity index. DCs from SS patients produced more IL-12 than those from the control. Likewise, IL-12 treatment in NOD mice significantly decreased salivary flow rates and promoted lymphocyte infiltration in salivary glands. IL-12 antibodies downregulated Th1, Th17, and Tfh cell. MSCT enhanced salivary flow rates and decreased lymphocyte infiltrations in salivary glands of NOD mice. MSCT downregulated Th17 and Tfh cells but upregulated regulatory T cells. MSCT reduced IL-12 productions in both SS patients and mice. Conclusion: Our results indicate that MSCs ameliorate SS possibly via suppressing IL-12 production in DCs and that IL-12 could be a potential therapeutic target of SS. Trial registration: NTC00953485. Registered June 2009.-
dc.languageeng-
dc.publisherBioMed Central Ltd. The Journal's web site is located at http://www.stemcellres.com-
dc.relation.ispartofStem Cell Research & Therapy-
dc.rightsStem Cell Research & Therapy. Copyright © BioMed Central Ltd.-
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.subjectInterleukin-12-
dc.titleMesenchymal stem cell transplantation ameliorates Sjögren’s syndrome via suppressing IL-12 production by dendritic cells-
dc.typeArticle-
dc.identifier.emailLu, L: liweilu@hku.hk-
dc.identifier.authorityLu, L=rp00477-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1186/s13287-018-1023-x-
dc.identifier.pmid30409219-
dc.identifier.pmcidPMC6225717-
dc.identifier.scopuseid_2-s2.0-85056429044-
dc.identifier.hkuros307254-
dc.identifier.volume9-
dc.identifier.spagearticle no. 308-
dc.identifier.epagearticle no. 308-
dc.publisher.placeUnited Kingdom-

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