干燥综合征小鼠中MDSCs数量及功能变化

The changes in number and function of MDSCs in Sj?gren’s syndrome mice

目的通过检测干燥综合征(Sjogren’s syndrome, SS)模型小鼠中髓系来源抑制性细胞(myeloid-derived suppressor cells,MDSCs)数量及功能变化,旨在揭示干燥综合征发病机制,并为其临床治疗提供新依据。方法本研究选取公认的非肥胖性糖尿病(non-obese diabetic,NOD)小鼠作为干燥综合征模型,分别检测4、8、10和12周龄NOD小鼠唾液流量变化;HE染色观察NOD小鼠颌下腺淋巴细胞浸润情况;并采用流式细胞术检测不同周龄NOD小鼠MDSCs数量及功能变化。结果随着NOD小鼠干燥综合征病情的发展,其唾液流量逐渐减少,颌下腺淋巴细胞浸润灶的数量及浸润面积明显增加;外周血中MDSCs比例显著升高;与对照组小鼠相比具有SS样症状的NOD小鼠MDSCs表面的未成熟标志物表达量明显降低。结论 MDSCs数量和功能伴随SS的发展而改变。靶向MDSCs可能成为干燥综合征患者治疗的新靶点。

The changes of number and function of myeloid-derived suppressor cells(MDSCs) were studied in Sjogren’s syndrome(SS) mice, for the purposes to provide new evidences for SS pathogenesis and clinical therapy.In this study, the non-obese diabetic(NOD) mice, as a valid mouse model for SS, were sacrificed at 4, 8, 10 and 12 weeks old, respectively. The salivary flow rate was detected;the lymphocytic infiltration in submandibular glands was detected by HE staining. The changes of number and function of MDSCs were determined by flow cytometric analysis in NOD mice of different ages. Data showed that along with the development of SS-like syndrome in NOD mice, the salivary flow rate decreased significantly and the number and area of lymphocytic infiltration foci increased significantly. The peripheral MDSCs increased significantly with age increase. Compared to control mice, the expression of immature or undifferentiated phenotype surface markers on splenic MDSCs decreased significantly in SS-like NOD mice. These findings suggested that MDSCs is increased and the MDSCs function is changed significantly with the development of SS-like syndrome in NOD mice, which might provide new targets for treatment of SS patients.