间质干细胞移植通过抑制树突状细胞产生 IL-12 改善干燥综合征。
Mesenchymal stem cell transplantation ameliorates Sjögren's syndrome via suppressing IL-12 production by dendritic cells.
机构信息
Department of Rheumatology and Immunology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China.
Department of Pathology and Center of Infection and Immunology, University of Hong Kong, Hong Kong, China.
出版信息
Stem Cell Res Ther. 2018 Nov 8;9(1):308. doi: 10.1186/s13287-018-1023-x.
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.
背景
间充质干细胞（MSCs）已被证明在治疗包括干燥综合征（SS）在内的自身免疫性疾病方面具有疗效。我们旨在比较 MSC 移植（MSCT）的效果和血清白细胞介素-12（IL-12）在 SS 中的作用。
方法
通过 ELISA 测定 IL-12 水平。通过 RT-PCR 测定树突状细胞（DCs）中的 IL-12 mRNA 转录物。在与 MSCs 共培养后，检测小鼠和人 DCs 中的 IL-12 mRNA 转录物。非肥胖型糖尿病（NOD）小鼠分别接受 MSCT、重组 IL-12 或抗 IL-12 mAb 治疗。然后，检查这些小鼠的唾液流量、唾液腺组织病理学和脾淋巴细胞亚群。
结果
SS 患者血清中的 IL-12 水平显著升高，并与 EULAR 2010 干燥综合征疾病活动指数呈正相关。来自 SS 患者的 DC 比来自对照的 DC 产生更多的 IL-12。同样，IL-12 处理 NOD 小鼠显著降低唾液流量并促进唾液腺中的淋巴细胞浸润。IL-12 抗体下调 Th1、Th17 和 Tfh 细胞。MSCT 增强 NOD 小鼠的唾液流量并减少唾液腺中的淋巴细胞浸润。MSCT 下调 Th17 和 Tfh 细胞，但上调调节性 T 细胞。MSCT 减少 SS 患者和小鼠中的 IL-12 产生。
结论
我们的结果表明，MSCs 通过抑制 DC 中 IL-12 的产生来改善 SS，并且 IL-12 可能是 SS 的潜在治疗靶点。
试验注册
NTC00953485。于 2009 年 6 月注册。
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