let-7e嵌合小鼠模型的建立和表型分析

Establishment of let-7e bone marrow chimeric mouse model and the analysis of immune phenotypes

目的:探讨微小RNA let-7e在淋巴细胞分化发育中的作用。方法:构建let-7e过表达嵌合小鼠模型,研究let-7e对淋巴组织中T细胞、B细胞、树突状细胞(DC)、髓系来源的抑制性细胞(MDSC)发育的影响;通过流式细胞仪检测MDSC的细胞增殖和细胞凋亡,初步探讨let-7e促使MDSC增多的机制。结果:嵌合小鼠模型检测结果显示:过表达let-7e后B细胞减少,浆细胞样DC(p DC)、经典DC(c DC)增多,而T细胞及亚群比例没有变化;同时,骨髓和脾脏中的MDSC比例升高,其凋亡水平明显降低,但其增殖没有改变。结论:let-7e参与了淋巴细胞的分化和发育;let-7e可以通过抑制细胞凋亡促进MDSC的增多。

Objective： To investigate the function of let-7e on the development of immunocytes. Methods： To study the function of let-7e on the development of immunocytes, the let-7e over-expression chimeric mouse were firstly established by retrovirus infection. Thereafter, the proliferation and apoptosis were evaluated by FACS. Results： Chimeric mouse model was successfully established and confirmed by FACS and qRT-PCR. FACS analysis showed that over-expressed let-7e decreased the percentage of B220 ＋ cells both in BM and spleen cells, increased the percentages of pDCs, cDCs,and MDSCs, but did not change the percentage of T cells and its subsets. Further experiments suggested that over-expressed let-Te increased the percentages of MDSCs by inhibiting the apoptosis of MDSCs, but did not alter their proliferation. Conclusion： let-7e is involved in lymphocyte differentiation and development; let-7e over-expression can increase the number of MDSCs by inhibiting apoptosis.