Interaction of dendritic cells and T lymphocytes for the therapeutic effect of Dangguiliuhuang decoction to autoimmune diabetes.
Interaction of dendritic cells and T lymphocytes for the therapeutic effect of Dangguiliuhuang decoction to autoimmune diabetes.
复制标题
树突状细胞与T淋巴细胞相互作用对当归六黄汤治疗自身免疫性糖尿病的影响
DOI：
10.1038/srep13982
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发表时间：
2015-09-11
影响因子：
4.6
通讯作者：
Xiang M
中科院分区：
文献类型：
--
作者：
Liu T;Cao H;Ji Y;Pei Y;Yu Z;Quan Y;Xiang M
当归六黄汤是治疗自身免疫性糖尿病的有效中药。在此，我们在非肥胖糖尿病（NOD）小鼠模型中研究了DGLHD的潜在抗糖尿病机制。在体外，DGLHD和单个活性成分增强HepG 2细胞中的葡萄糖摄取，抑制T淋巴细胞增殖，并抑制树突状细胞（DC）功能。在体内，DGLHD显着抑制胰岛炎，延缓糖尿病的发病和发展，促进胰岛素分泌和敏感性，并平衡部分正常化的Th 1和Th 2细胞因子在NOD小鼠。此外，DGLHD还可增加胰腺、脾脏、胸腺、DCs和NIT-1细胞中α1-抗胰蛋白酶（AAT-1）、Bcl-2和CyclinD 1的表达，降低Bax的表达，这与保护和修复胰岛β细胞的作用一致。更详细的研究表明，DGLHD调节DC的成熟和功能，降低部分细胞树突状细胞（mcDC）亚群的百分比，并增加DC中程序性死亡配体-1（PD-L1）的表达。DGLHD在体内也抑制T淋巴细胞增殖并促进调节性T细胞（Tcells）分化。JAK 2-STAT 3依赖性通路参与了DGLHD抑制DC与T淋巴细胞相互作用的过程。实验表明，五种活性成分参与了DGLHD的特异性抗糖尿病作用。结果表明，配方组成合理。
In traditional Chinese medicine (TCM), Dangguiliuhuang decoction (DGLHD) is an effective treatment of autoimmune diabetes. Here, we studied potential anti-diabetic mechanisms of DGLHD in a non-obese diabetic (NOD) mouse model. In vitro, DGLHD and individual active ingredients enhanced glucose uptake in HepG2 cells, inhibited T lymphocyte proliferation, and suppressed dendritic cells (DCs) function. In vivo, DGLHD significantly inhibited insulitis, delayed the onset and development of diabetes, promoted insulin secretion and sensitivity, and balanced partially normalized Th1 and Th2 cytokines in NOD mice. In addition, DGLHD increased α1-antitrypsin (AAT-1), Bcl-2, and CyclinD1, and decreased Bax levels in pancreas, spleen, thymus, DCs, and a NIT-1 cell line, all consistent with protecting and repairing islet β cell. More detailed studies indicated that DGLHD regulated the maturation and function of DCs, decreased the percentage of merocytic dendritic cells (mcDCs) subset, and increased programmed death ligand-1 (PD-L1) expression in DCs. DGLHD also impeded T lymphocyte proliferation and promoted regulatory T cells (Tregs) differentiation in vivo. A JAK2-STAT3-dependent pathway was involved in the suppression by DGLHD of interactions between DCs and T lymphocyte. The experiments implicated five active ingredients in specific anti-diabetic actions of DGLHD. The results demonstrated the reasonable composition of the formula.