Lee Jong Joo, Jeong Hyun Jeong, Kim Mee Kum, Wee Won Ryang, Lee Won Woo, Kim Seung U, Sung Changmin, Yang Yung Hun
Department of Ophthalmology, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 110-799, South Korea.
Purinergic Signal. 2014;10(2):357-65. doi: 10.1007/s11302-013-9385-0. Epub 2013 Sep 17.
This study investigated the immune-modulatory effects of human bone marrow-derived mesenchymal stem cells (hBMSCs) on human Th17 cell function through the CD39-mediated adenosine-producing pathway. The suppressive effects of hBMSCs were evaluated by assessing their effects on the proliferation of Th17 cells and the secretion of interferon (IFN)-γ and interleukin (IL)-17A by Th17 cells with or without anti-CD39 treatment. Changes in CD39 and CD73 expression on the T cells with or without co-culture of hBMSCs were evaluated by flow cytometry. hBMSCs effectively suppressed the proliferation of Th17 cells and the secretion of both IL-17A and IFN-γ from Th17 cells using by both flow cytometry and ELISA, while anti-CD39 treatment significantly reduced the inhibitory effects of hBMSCs on the proliferation and secretion of the Th17 cells. The hBMSCs induced increased expression of the CD39 and CD73 on T cells correlated with the suppressive function of hBMSCs, which was accompanied by increased adenosine production. Our data suggests that hBMSCs can effectively suppress immune responses of the Th17 cells via the CD39-CD73-mediated adenosine-producing pathway.
本研究通过CD39介导的腺苷生成途径,研究了人骨髓间充质干细胞(hBMSCs)对人Th17细胞功能的免疫调节作用。通过评估hBMSCs对Th17细胞增殖以及在有或无抗CD39处理情况下Th17细胞分泌干扰素(IFN)-γ和白细胞介素(IL)-17A的影响,来评价hBMSCs的抑制作用。通过流式细胞术评估有或无hBMSCs共培养情况下T细胞上CD39和CD73表达的变化。利用流式细胞术和酶联免疫吸附测定(ELISA),hBMSCs有效抑制了Th17细胞的增殖以及Th17细胞分泌IL-17A和IFN-γ,而抗CD39处理显著降低了hBMSCs对Th17细胞增殖和分泌的抑制作用。hBMSCs诱导T细胞上CD39和CD73表达增加,这与hBMSCs的抑制功能相关,同时伴有腺苷生成增加。我们的数据表明,hBMSCs可通过CD39-CD73介导的腺苷生成途径有效抑制Th17细胞的免疫反应。