Journal
STEM CELL RESEARCH & THERAPY
Volume 9, Issue -, Pages -Publisher
BMC
DOI: 10.1186/s13287-018-1023-x
Keywords
Mesenchymal stem cells; Sjogren's syndrome; Interleukin-12
Funding
- National Natural Science Foundation of China (NSFC) [81571583, 81770061]
- Major International (Regional) Joint Research Project [81720108020]
- Jiangsu Province Major Research and Development Program [BE2015602]
- China National Natural Science Foundation [91442119]
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BackgroundMesenchymal stem cells (MSCs) have been demonstrated to be effective in treating autoimmune diseases including Sjogren's syndrome (SS). We aim to compare the effects of MSC transplantation (MSCT) and the role of serum interleukin-12 (IL-12) in SS.MethodsIL-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.ResultsIL-12 levels in the serum were significantly increased in SS patients and positively correlated with the EULAR 2010 Sjogren'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.ConclusionOur 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 registrationNTC00953485. Registered June 2009.
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