IL-10上调PD-1配体的表达诱导耐受性树突状细胞形成

目的 探讨IL-10诱导耐受性树突状细胞（DCs）形成的机制。方法 用30ng／mL的IL-10处理Balb／c小鼠骨髓DCs，分别用RT-PCR和流式细胞术分析DCs的PD-1配体分子的表达，用MTF法测定DCs激活T细胞的能力，并用IL-10-DCs免疫荷瘤小鼠，观察H22肝癌细胞的生长情况。结果 IL-10-DCs对T细胞的激活能力降低；在注射了IL-10-DCs的小鼠体内，H22肝癌细胞的生长速度快于对照组；免疫抑制性受体PD-1的配体分子在IL-10-DCs上的表达上调。结果提示，在H22肝癌模型上，IL-10上调PD-1的配体分子表达可能是免疫耐受的一个机制。结论 减少IL-10的产生或封闭PD-1／PD-L路径可能是一个很有前景的肝癌生物学治疗策略。

IL-10 induces formation of tolerogenic dendritic cells by upregulating PD-1 ligand expression

Objective To investigate the mechanism of tolerogenic dendritic cells(DCs) formation induced by IL-10.Methods Mouse bone marrow-derived dendritic cells were treated by IL-10(30 ng/mL).The ligands of PD-1(PD-L1 and PD-L2) were analyzed by RT-PCR and Flow cytometry.Activation of spleen lymphocytes were detected by MTT colorimetry.The BALB/c mice loaded with H22 cells were immunized with IL-10-treated dendritic cells and the growth of H22 cells in mice was evaluated.Results The activation of spleen lymphocytes stimulated by IL-10-treated DCs was decreased in vitro.The growth of H22 cells in mice immunized with IL-10-treated dendritic cells was much faster than that in mice immunized with dendritic cells.The expressions of PD-L1 and PD-L2 were upregulated by IL-10.All results suggested that overexpression of PD-1 ligands on DCs could be a mechanism of IL-10-induced immunotolerance in model of BALB/c mice loaded with H22 cells.Conclusion Inhibiting the production of IL-10 and Blocking PD-1/PD-L1 pathway may be promising strategies for hepatocellular carcinoma therapy.