Zhao Yulei, Su Guohong, Wang Qing, Wang Ruihuan, Zhang Minjuan
The Second Department of Hematology, Cangzhou Central Hospital 16 West Xinhua Road, Yunhe, Cangzhou, China.
Am J Transl Res. 2021 Aug 15;13(8):9607-9613. eCollection 2021.
To investigate the CD200/CD200R pathway mechanism in mesenchymal stem cells' (MSC) regulation of dendritic cells (DC) (MSc).
We collected marrow samples from 40 patients admitted to our hospital from January 2018 to December 2019. The bone marrow MSCs were cultivated, and the peripheral blood mononuclear cells (PBMC) and peripheral blood DC were isolated to establish an in vitro immune response model. The expressions of the CD200 molecule on the surface of MSC were measured. Anti-CD200 blocking antibodies were added to the culture system to observe the effect of the PBMC differentiation and the immature DC (imDC) to mature DC (mDC). Then the impact of the different positive rates of CD200 in the same MSC on imDC maturity was measured.
After adding mitogen pHA, the IL-4, IL-10, and TNF-α secretions were increased (all P<0.05), and the OD value of the PBMC+pHA group was higher than it was in the PBMC group. After stimulated by pHA, the CD200 of the MSC group was higher than it was in the MSC+PBMC group (P<0.05). The MSC+PBMC group co-culture inhibited the development of imDC to mDC. Adding anti-CD200 antibodies to the MSC+PBMC co-culture system, MSC could still inhibit the differentiation of PBMC to imDC, and MSC had a significant inhibition effect on imDC to mDC maturation (P=0.006). The addition of MSC reduces the maturation markers on the surface of mDC (P<0.05). The addition of MSC inhibited the ability of mDC to stimulate PBMC (P<0.05) and decreased the IL-12 (P<0.05) levels. The addition of the anti-CD200 antibody increased the proliferation ability of mDC to stimulate PBMC (P<0.05), and it also increased the IL-12 levels in mDC (P<0.05). The expression of the DC mature immune phenotype in the CD200 high expression group was weak (P<0.05).
The mechanism by which MSC inhibits DC may be achieved through the CD200/CD200R pathway, and the CD200/CD200R pathway mainly acts on the process from imDC to mDC.
探讨间充质干细胞（MSC）调控树突状细胞（DC）过程中的CD200/CD200R通路机制。
收集2018年1月至2019年12月我院收治的40例患者的骨髓样本。培养骨髓间充质干细胞，分离外周血单个核细胞（PBMC）和外周血DC，建立体外免疫反应模型。检测间充质干细胞表面CD200分子的表达。在培养体系中加入抗CD200阻断抗体，观察PBMC分化及未成熟DC（imDC）向成熟DC（mDC）分化的影响。然后检测同一间充质干细胞中不同CD200阳性率对imDC成熟的影响。
加入丝裂原pHA后，IL-4、IL-10和TNF-α分泌增加（均P<0.05），PBMC+pHA组的OD值高于PBMC组。pHA刺激后，MSC组的CD200高于MSC+PBMC组（P<0.05）。MSC+PBMC组共培养抑制imDC向mDC的发育。在MSC+PBMC共培养体系中加入抗CD200抗体，MSC仍可抑制PBMC向imDC的分化，且MSC对imDC向mDC成熟有显著抑制作用（P=0.006）。加入MSC可降低mDC表面的成熟标志物（P<0.05）。加入MSC抑制mDC刺激PBMC的能力（P<0.05），并降低IL-12水平（P<0.05）。加入抗CD200抗体增加mDC刺激PBMC的增殖能力（P<0.
