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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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Detalles Bibliográficos
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
Descripción
Sumario: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.