华北理工大学,北京大学医学部实验动物科学部,华北理工大学,北京大学医学部实验动物科学部,北京大学医学部实验动物科学部,唐山市工人医院,华北理工大学,华北理工大学,华北理工大学,华北理工大学,中国科学院动物研究所,华北理工大学
国家自然科学基金面上项目 (81373111, 81673208)资助
North China University of Science and Technology,Department of laboratory animal science, Pecking University Health Science Center,North China University of Science and Technology,Department of laboratory animal science, Pecking University Health Science Center,Department of laboratory animal science, Pecking University Health Science Center,Tangshan Gongren Hospital,North China University of Science and Technology,North China University of Science and Technology,North China University of Science and Technology,North China University of Science and Technology,Institute of Zoology, Chinese Academy of Sciences,North China University of Science and Technology
This work was supported by a grant from The National Natural Science Foundation of China (81373111, 81673208)
为探讨组蛋白去乙酰化酶3(HDAC3)在T细胞自稳中的作用,采用LoxP-cd4cre酶系统在胸腺CD4+CD8+双阳性T细胞(DP)中敲除hdac3基因.hdac3基因敲除小鼠不影响T细胞在胸腺中的发育,但导致外周T细胞显著降低,而且,hdac3基因敲除的外周T细胞主要以活化/效应/记忆表型为主.机制分析表明,hdac3基因敲除的外周T细胞凋亡增加并伴随细胞增殖加速,同时,Fas 和Fas配体阳性细胞比率以及Fas配体的表达显著增加.体外TCR活化不影响正常外周T细胞的凋亡,但导致hdac3基因敲除的外周T细胞凋亡显著增加.实验结果表明,HDAC3通过抑制活化诱导的细胞凋亡维持外周T细胞自稳.
To investigate the role of histone deacetylase3(HDAC3) in T cell homeostasis, we deleted hdac3 in CD4+CD8+ double positive(DP) stage of thymocytes using the cd4-cre transgene .The CD4Cre-mediated hdac3 deletion did not impact T cell development in the thymus but resulted in a dramatic loss of peripheral T cells. In addition, peripheral T cells in hdac3 knock-out mice showed a dominant activation/effector/memory phenotype. Mechanism analysis revealed an increased cell apoptosis which was accompanied by an accelerated cell proliferation in the peripheral T cells of hdac3 knock-out mice. Moreover, Fas and FasL positive cells and FasL expression increased significantly in the peripheral T cells of hdac3 knock-out mice. In vitro TCR activation did not affect the apoptosis of normal peripheral T cells, but dramatically increased apoptosis of peripheral T cells from hdac3 knock-out mice. Our results presented here indicate an important role of HDAC3 in maintaining homeostasis of peripheral T cells by refraining them from activation- induced cell death.
王姗,田枫,千晔,刘颖,李会婷,张爱红,侯志宏,刘亚楠,李娟,张艳淑,赵勇,郑全辉.组蛋白去乙酰化酶3通过抑制AICD维持T细胞自稳[J].生物化学与生物物理进展,2018,45(1):79-90
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