1型糖尿病小鼠体内树突状细胞亚群变化的初步研究

Changes in dendritic cell subsets in mice with type 1 diabetes mellitus

目的探讨1型糖尿病（type 1 diabetes mellitus, T1DM）发病过程中外周免疫器官DC亚群的改变。方法以尾静脉注射链脲佐菌素（streptozotocin，STZ）的方式制备糖尿病小鼠模型。在STZ处理后的不同时间，检测小鼠体重变化和血糖水平；制备脾脏和淋巴结单细胞，通过流式细胞术检测DC亚群、中性粒细胞、单核细胞、CD4＋Foxp3＋调节性T细胞（regulatory T cells, Treg）的比例。结果STZ处理可导致小鼠体重减轻、血糖升高。在STZ处理后10 d，T1DM小鼠脾脏和淋巴结中DC各亚群、中性粒细胞和单核细胞的比例均未发生显著改变；STZ处理后30 d和60 d，T1DM小鼠脾脏体积明显减少，DC各亚群的比例较正常小鼠降低，中性粒细胞和单核细胞的比例则上调；而在淋巴结中，DC各亚群、中性粒细胞和单核细胞的比例较正常对照均显著下调。同时，与正常对照相比，淋巴结中的CD4＋Foxp3＋Treg比例明显上调，但在脾脏中无明显变化。结论在STZ诱导的小鼠糖尿病模型中，DC亚群及其他炎症细胞在脾脏和淋巴结中发生明显改变，反映了T细胞的变化，提示DC亚群在T1DM发病中起重要作用。

ObjectiveTo investigate the changes in dendritic cell （DC） subsets in mice with type 1 diabetes mellitus （T1DM）.MethodsA mouse model of diabetes was established through intravenous injection of streptozotocin （STZ） solution. At different time points after STZ treatment, changes in body weight and blood glucose level were observed. Flow cytometry analysis was performed to detect DC subsets, neutrophils, monocytes and CD4＋ Foxp3＋ regulatory T cells （Treg） in spleen and lymph nodes.ResultsSTZ treatment led to weight loss and increase in blood glucose in mice. Ten days after STZ treatment, no significant difference in the percentages of DC subsets, neutrophils and monocytes in both spleen and lymph nodes was found between T1DM mice and normal controls. However, spleen volume in the mice treated by STZ significantly reduced, and the percentages of DC subsets in spleen decreased whereas the percentages of neutrophils and monocytes increased as compared with those of normal controls on 30 d and 60 d. Moreover, the percentages of DC subsets, neutrophils and monocytes in lymph nodes of STZ-treated mice were significantly lower than those of normal controls. Meanwhile, the percentage of CD4＋ Foxp3＋ Treg cells in lymph nodes but not in spleen was significantly upregulated as compared with that of normal controls.ConclusionSignificant changes in DC subsets and other inflammatory cells in spleen and lymph nodes are observed in mice with STZ-induced diabetes, which reflects the changes in T cell responses and suggests that DC subsets might play an important role in the pathogenesis of T1DM.