Mesenchymal stem cell transplantation ameliorates Sjögren's syndrome via suppressing IL-12 production by dendritic cells.
Mesenchymal stem cell transplantation ameliorates Sjögren's syndrome via suppressing IL-12 production by dendritic cells.
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间充质干细胞移植通过抑制树突状细胞产生 IL-12 来改善干燥综合征
DOI：
10.1186/s13287-018-1023-x
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发表时间：
2018-11-08
影响因子：
7.5
通讯作者：
Sun L
中科院分区：
文献类型：
--
作者：
Shi B;Qi J;Yao G;Feng R;Zhang Z;Wang D;Chen C;Tang X;Lu L;Chen W;Sun L
间充质干细胞（MSCs）已被证明可有效治疗自身免疫性疾病，包括Sjögren综合征（SS）。我们的目的是比较间充质干细胞移植（MSCT）和血清白细胞介素-12 （IL-12）在SS中的作用。RT-PCR检测树突状细胞（DCs） IL-12 mRNA转录物。与MSCs共培养后，检测小鼠和人dc中IL-12 mRNA转录物。非肥胖糖尿病（NOD）小鼠分别接受MSCT、重组IL-12或抗IL-12单抗治疗。然后，检测这些小鼠的唾液流速、唾液腺的组织病理学和脾淋巴细胞亚群。SS患者血清IL-12水平显著升高，且与EULAR 2010 Sjögren综合征疾病活动指数呈正相关。来自SS患者的dc比来自对照组的dc产生更多的IL-12。同样，IL-12处理NOD小鼠的唾液流率显著降低，并促进唾液腺淋巴细胞浸润。IL-12抗体下调Th1、Th17和Tfh细胞。MSCT增强NOD小鼠唾液腺的唾液流率，减少淋巴细胞浸润。MSCT下调Th17和Tfh细胞，上调调节性T细胞。MSCT降低了SS患者和小鼠IL-12的产生。我们的研究结果表明，MSCs可能通过抑制dc中IL-12的产生来改善SS， IL-12可能是SS. NTC00953485的潜在治疗靶点。2009年6月注册。本文的在线版本（10.1186/s13287-018-1023-x）包含补充内容，授权用户可以使用。
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. 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. 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. 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. NTC00953485. Registered June 2009. 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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影响因子：
12.8
作者：
Gottenberg, JE;Lavie, F;Mariette, X
通讯作者：
Mariette, X
影响因子：
4.4
作者：
Nauta, Alma J.;Kruisselbrink, Alwine B.;Fibbe, Willem E.
通讯作者：
Fibbe, Willem E.
影响因子：
--
作者：
Ohyama, Y;Nakamura, S;Nomoto, K
通讯作者：
Nomoto, K
影响因子：
6.2
作者：
Ramasamy, Rajesh;Fazekasova, Henrietta;Dazzi, Francesco
通讯作者：
Dazzi, Francesco
影响因子：
6
作者：
Katsifis, Gikas E.;Rekka, Sofia;Wahl, Sharon M.
通讯作者：
Wahl, Sharon M.