Immunomodulatory Function of Regulatory Dendritic Cells Induced by Mesenchymal Stem Cells
Immunomodulatory Function of Regulatory Dendritic Cells Induced by Mesenchymal Stem Cells
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间充质干细胞诱导的调节性树突状细胞的免疫调节功能
DOI：
10.3109/08820139.2011.607877
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发表时间：
2012-01-01
影响因子：
2.8
通讯作者：
Zou, Ping
中科院分区：
文献类型：
--
作者：
Zhao, Zhi-Gang;Xu, Wen;Zou, Ping
间充质干细胞（MSCs）为干细胞治疗方法的开发提供了一个极佳的模型，在证实其对T细胞甚至树突状细胞（DCs）之间复杂相互作用具有免疫调节作用之后，其在免疫致病性疾病中的潜在治疗作用引起了更多关注。然而，人们对MSCs这些免疫调节作用的潜在机制知之甚少。在本研究中，我们发现骨髓来源的MSCs能够将成熟DCs（mDCs）分化为一种独特的调节性DC群体。与mDCs相比，它们的CD1a、CD80、CD86和CD40表达较低，但CD11b表达较高。MSCs诱导的DCs（MSC - DCs）即使在受到脂多糖（LPS）刺激时也几乎不能刺激T细胞增殖。此外，还观察到MSC - DCs具有高内吞能力、低免疫原性和强免疫调节功能。而且，MSC - DCs能够有效地从CD4⁺CD25⁻Foxp3⁻T细胞生成CD4⁺CD25⁺Foxp3⁺调节性T细胞。MSC - DCs的抑制功能不仅通过转化生长因子 - β1介导，还通过诱导调节性T细胞的产生或T细胞无能来介导。这些结果表明，MSCs诱导的调节性DCs的免疫调节作用为免疫致病性疾病提供了有效的治疗方法。
Mesenchymal stem cells (MSCs) provide an excellent model for development of stem cell therapeutics, and their potential treatment in the immunopathogenic diseases have gained further interest after demonstration of immunomodulatory effects on complicated interactions between T cells and even dendritic cells (DCs). However, the mechanisms underlying these immunoregulatory effects of MSCs are poorly understood. In this study, we show that bone marrow derived MSCs can differentiate mature DCs (mDCs) into a distinct regulatory DC population. Compared with mDCs, they have lower expression of CD1a, CD80, CD86 and CD40, but higher expression of CD11b. MSCs induced DCs (MSC-DCs) can hardly stimulate T-cell proliferation even when MSC-DCs are stimulated by LPS. In addition, high endocytosic capacity, low immunogenicity, and strong immunoregulatory function of MSC-DCs are also observed. Moreover, MSC-DCs can efficiently generate CD4+CD25+Foxp3+ Treg cells from CD4+CD25-Foxp3-T cells. The inhibitory function of MSC-DCs is mediated not only through TGF-beta 1, but also by inducing the production of Treg cells or T-cell anergy. These results demonstrate that the immunomodulatory effects of regulatory DCs induced by MSCs provide efficacious treatment for immunopathogenic diseases.