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

BACKGROUND: 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 E...

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Autores principales: Shi, Bingyu, Qi, Jingjing, Yao, Genhong, Feng, Ruihai, Zhang, Zhuoya, Wang, Dandan, Chen, Chen, Tang, Xiaojun, Lu, Liwei, Chen, Wanjun, Sun, Lingyun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6225717/
https://www.ncbi.nlm.nih.gov/pubmed/30409219
http://dx.doi.org/10.1186/s13287-018-1023-x
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author Shi, Bingyu
Qi, Jingjing
Yao, Genhong
Feng, Ruihai
Zhang, Zhuoya
Wang, Dandan
Chen, Chen
Tang, Xiaojun
Lu, Liwei
Chen, Wanjun
Sun, Lingyun
author_facet Shi, Bingyu
Qi, Jingjing
Yao, Genhong
Feng, Ruihai
Zhang, Zhuoya
Wang, Dandan
Chen, Chen
Tang, Xiaojun
Lu, Liwei
Chen, Wanjun
Sun, Lingyun
author_sort Shi, Bingyu
collection PubMed
description BACKGROUND: 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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13287-018-1023-x) contains supplementary material, which is available to authorized users.
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spelling pubmed-62257172018-11-19 Mesenchymal stem cell transplantation ameliorates Sjögren’s syndrome via suppressing IL-12 production by dendritic cells Shi, Bingyu Qi, Jingjing Yao, Genhong Feng, Ruihai Zhang, Zhuoya Wang, Dandan Chen, Chen Tang, Xiaojun Lu, Liwei Chen, Wanjun Sun, Lingyun Stem Cell Res Ther Research BACKGROUND: 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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13287-018-1023-x) contains supplementary material, which is available to authorized users. BioMed Central 2018-11-08 /pmc/articles/PMC6225717/ /pubmed/30409219 http://dx.doi.org/10.1186/s13287-018-1023-x Text en © The Author(s). 2018 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Shi, Bingyu
Qi, Jingjing
Yao, Genhong
Feng, Ruihai
Zhang, Zhuoya
Wang, Dandan
Chen, Chen
Tang, Xiaojun
Lu, Liwei
Chen, Wanjun
Sun, Lingyun
Mesenchymal stem cell transplantation ameliorates Sjögren’s syndrome via suppressing IL-12 production by dendritic cells
title Mesenchymal stem cell transplantation ameliorates Sjögren’s syndrome via suppressing IL-12 production by dendritic cells
title_full Mesenchymal stem cell transplantation ameliorates Sjögren’s syndrome via suppressing IL-12 production by dendritic cells
title_fullStr Mesenchymal stem cell transplantation ameliorates Sjögren’s syndrome via suppressing IL-12 production by dendritic cells
title_full_unstemmed Mesenchymal stem cell transplantation ameliorates Sjögren’s syndrome via suppressing IL-12 production by dendritic cells
title_short Mesenchymal stem cell transplantation ameliorates Sjögren’s syndrome via suppressing IL-12 production by dendritic cells
title_sort mesenchymal stem cell transplantation ameliorates sjögren’s syndrome via suppressing il-12 production by dendritic cells
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6225717/
https://www.ncbi.nlm.nih.gov/pubmed/30409219
http://dx.doi.org/10.1186/s13287-018-1023-x
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