Xiangya Stomatological Hospital and School of Stomatology, Central South University, Changsha, Hunan, China.
Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, Capital Medical University School of Stomatology, Beijing, China.
Cell Prolif. 2019 May;52(3):e12595. doi: 10.1111/cpr.12595. Epub 2019 Apr 5.
Mesenchymal stem cells (MSCs) could regulate the function of various immune cells. It remains unclear whether MSCs additionally possess immunostimulatory properties. We investigated the impact of human MSCs on the responsiveness of primary natural killer (NK) cells in terms of induction of anti-inflammatory purinergic signalling.
We obtained human bone marrow mesenchymal stem cells (BMMSCs) and dental pulp stem cells (DPSCs). NK cells were isolated from peripheral blood of healthy volunteers. Activated NK cells were cultured with MSCs. Proliferation assay, apoptosis analysis, activating or inhibitory receptor expression and degranulation assay were used to explore NK cells' function. High-performance liquid chromatography was used to investigate the purinergic signalling in activated NK cells.
Both DPSCs and BMMSCs could impair proliferation and promote apoptosis of activated NK cells. Also, activated NK cells could cause DPSCs to lyse. Furthermore, the expression of activating NK cells' receptors was decreased, but inhibitory receptors of NK cells were elevated following co-cultivation. NK cells acquired CD73 expression, while MSCs could release ATP into the extracellular space where nucleotides were converted into adenosine (ADO) following co-culture system. Under the existence of exogenous 2-chloroadenosine (CADO), the cytotoxic capacity of NK cells was remarkably depressed in a concentration-dependent manner.
DPSCs and BMMSCs could depress NK cells' function by hydrolysing ATP to ADO using CD39 and CD73 enzymatic activity. Our data suggested that DPSCs might represent a new strategy for treating immune-related diseases by regulating previously unrecognized functions in innate immune responses.
间充质干细胞（MSCs）可以调节各种免疫细胞的功能。目前尚不清楚 MSCs 是否具有免疫刺激特性。我们研究了人 MSCs 对原发性自然杀伤（NK）细胞反应性的影响，特别是在诱导抗炎嘌呤能信号方面。
我们获得了人骨髓间充质干细胞（BMMSCs）和牙髓干细胞（DPSCs）。NK 细胞从健康志愿者的外周血中分离出来。用 MSCs 培养激活的 NK 细胞。增殖试验、凋亡分析、激活或抑制性受体表达和脱颗粒试验用于探索 NK 细胞的功能。高效液相色谱法用于研究激活的 NK 细胞中的嘌呤能信号。
DPSCs 和 BMMSCs 均可抑制激活的 NK 细胞增殖并促进其凋亡。此外，激活的 NK 细胞可导致 DPSCs 裂解。此外，共培养后 NK 细胞激活受体的表达减少，但抑制性受体的表达增加。NK 细胞获得了 CD73 的表达，而 MSC 可以将 ATP 释放到细胞外空间，在共培养系统中核苷酸转化为腺苷（ADO）。在存在外源性 2-氯腺苷（CADO）的情况下，NK 细胞的细胞毒性能力以浓度依赖的方式显著降低。
DPSCs 和 BMMSCs 可以通过 CD39 和 CD73 酶活性将 ATP 水解为 ADO 来抑制 NK 细胞的功能。我们的数据表明，DPSCs 可能通过调节先天免疫反应中以前未被认识到的功能，为治疗免疫相关疾病提供一种新策略。
