Notch1信号调控小鼠胸腺T细胞凋亡的机制研究

Notch1 signaling regulates apoptosis of thymic T lymphocytes

目的:Notch1基因介导的信号传递系统对哺乳动物胸腺T细胞的发育极为重要,而细胞凋亡是T细胞分化和成熟过程中重要的调控方式,Notch1对小鼠胸腺T细胞凋亡的影响。方法:应用Notch1基因配体结合域点突变小鼠的胸腺T细胞以及突变小鼠胸腺T细胞和OP9-DL细胞共培养体系,研究Notch1对小鼠胸腺T细胞自发和诱导性凋亡的影响。结果:Notch1胞外段点突变后,Notch1信号转导能力降低,胸腺T淋巴细胞的自发性凋亡、诱导凋亡以及配体介导下的细胞凋亡等均有所增加;此外,Notch1信号传递能力的降低增强了促凋亡基因的表达而降低凋亡抑制基因的表达。结论:Notch1和配体相互作用通过凋亡相关基因的表达参与T细胞凋亡的调控。

Objective：Notchl signaling plays important roles during development and maturation of T lymphocytes in thymus, whereas the apoptosis involved. The study evaluates the connection of Notchl on apoptosis ofT lymphocytes in mice thymus. Methods： The effects of Notchl on the spontaneous and induced apoptosis of T lymphocytes were investigated using mice with a point mutation in Notch1 ligand binding domain. T lymphocytes were isolated and cultured alone or co-cultured with OP9-DL stromal cells. Apoptosis of the T lymphocytes were measured by FACS, expression of apoptosis related genes were analyzed by RT-PCR. Results ： Notchl signaling was reduced significantly in mutant mice. Spontaneous and induced apoptosis of T lymphocytes were enhanced in DP subpopulation, the expression of pro-apoptotic genes were increased hut anti-apoptotic were decreased. Conclusion ： Notchl-ligand interaction regulates T lymphocytes apoptosis in thymus by regulating apoptosis related genes.