颗粒蛋白前体通过CTLA4调控调节性T细胞的发育和功能

Progranulin modulates the differentiation and function of regulatory T cell through CTLA4

目的探讨颗粒蛋白前体(PGRN)对调节性T细胞发育和功能的影响及分子机制。方法在野生型和PGRN敲除小鼠模型中,采用流式细胞术检测小鼠中枢及外周各淋巴器官中T细胞各亚群的比例及调节性T细胞比例及其功能相关分子的表达;采用RT-PCR检测调节性T细胞中CTLA4的表达;最后采用调节性T细胞体外抑制试验验证其功能变化。结果与野生型小鼠相比,PGRN敲除小鼠脾脏、胸腺和淋巴结中调节性T细胞的比例均升高,特别发现在脾脏调节性T细胞中CTLA4在基因和蛋白表达水平均显著升高。体外功能试验发现PGRN敲除小鼠的脾脏调节性T细胞的抑制功能也较野生型增强。结论 PGRN在调节性T细胞的发育和功能中扮演重要角色,其机制可能涉及CTLA4。

This study was designed to investigate the effect of progranulin(PGRN)on the differentiation and function of regulatory T cell,and the molecule mechanism.Flow cytometry was used to detect the subpopulations of T cell,the ratio of regulatory T cell and function-related molecules in wildtype and PGRN knockout mice.Realtime PCR was used to detect the expression of CTLA4 in regulatory T cell.Regulatory T cell suppression assay in vitro were used to verify the functional changes.Compared with wildtype mice,the proportion of regulatory T cell in spleen,thymus and lymph nodes of PGRN knockout mice was increased,and the mRNA and protein expression of CTLA4 were increased in splenic Treg.The in vitro function tests shown that the suppression function of regulatory T cell was also enhanced compared to that of wildtype.In conclusion,PGRN plays an important role in the differentiation and function of regulatory T cell,and the mechanism may related with CTLA4.