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牙髓干细胞通过转化生长因子-β1抑制淋巴细胞的增殖。

Dental pulp stem cells suppress the proliferation of lymphocytes via transforming growth factor-β1.

作者信息

Ding Gang, Niu Jianyi, Liu Yi

机构信息

Department of Stomatology, Yidu Central Hospital, Weifang Medical University, Linglongshan South Road No. 4138, Qingzhou, 262500, Shandong, People's Republic of China,

出版信息

Hum Cell. 2015 Apr;28(2):81-90. doi: 10.1007/s13577-014-0106-y. Epub 2015 Jan 21.

Abstract

Dental pulp stem cells (DPSCs) possess self-renewal capability, multi-lineage differentiation potential, and can generate a dentin-pulp-like tissue in vivo, which is promising for tooth regeneration. To enlarge the cells resource of DPSCs and explore the feasibility of DPSCs-mediated immune therapy, it is prerequisite to investigate the immunological properties of DPSCs and the underlying mechanisms. Human DPSCs and peripheral blood mononuclear cells were isolated and cultured. Then we used lymphocytes proliferation assays, cytokines detection, Transwell cultures, neutralization experiments, and flow cytometry to examine the in vitro immune characteristics of DPSCs. We found that DPSCs failed to stimulate allogeneic T cells proliferation and suppressed T cells proliferation, B cells proliferation, and mixed lymphocyte reaction. In addition, DPSCs could up-regulate IL-10, down-regulate the production of IL-2, IL-17, and IFN-γ, and did not affect the production of IL-6. Monoclonal antibody against transforming growth factor-β1 restored the T cells proliferation inhibited by DPSCs. Moreover, the population of regulatory T cells increased significantly and T-helper 17 cells decreased significantly in peripheral blood mononuclear cells co-cultured with DPSCs. These data confirmed that DPSCs are low immunogenic, could inhibit the proliferation of lymphocytes, regulate the production of cytokines in vitro, and the secretion of transforming growth factor-β1 may be involved in this event.

摘要

牙髓干细胞(DPSCs)具有自我更新能力、多向分化潜能,并且能够在体内生成牙本质-牙髓样组织,这为牙齿再生带来了希望。为了扩大DPSCs的细胞来源并探索DPSCs介导的免疫治疗的可行性,研究DPSCs的免疫学特性及其潜在机制是必要的。分离并培养了人DPSCs和外周血单个核细胞。然后我们使用淋巴细胞增殖试验、细胞因子检测、Transwell培养、中和实验和流式细胞术来检测DPSCs的体外免疫特性。我们发现DPSCs未能刺激同种异体T细胞增殖,反而抑制T细胞增殖、B细胞增殖以及混合淋巴细胞反应。此外,DPSCs能够上调IL-10,下调IL-2、IL-17和IFN-γ的产生,并且不影响IL-6的产生。抗转化生长因子-β1单克隆抗体恢复了被DPSCs抑制的T细胞增殖。而且,与DPSCs共培养的外周血单个核细胞中调节性T细胞群体显著增加,辅助性T细胞17显著减少。这些数据证实DPSCs免疫原性低,能够抑制淋巴细胞增殖,在体外调节细胞因子的产生,并且转化生长因子-β1的分泌可能参与了这一过程。

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