The epigenetic modification during the induction of Foxp3 with sodium butyrate
The epigenetic modification during the induction of Foxp3 with sodium butyrate
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DOI：
10.1080/08923973.2018.1480631
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发表时间：
2018-01-01
影响因子：
3.3
通讯作者：
Muhammad, Abbas
中科院分区：
文献类型：
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作者：
Cao, Tengli;Zhang, Xiuxiu;Muhammad, Abbas
背景：CD4+CD25+ 调节性 T (Treg) 淋巴细胞对于免疫稳态至关重要。 Foxp3（Forkhead Box蛋白P3）因其在Treg细胞中的特殊性，一直被认为是决定Treg细胞功能和身份的标志物。缺乏Treg细胞或Foxp3基因低表达的人会遭受致命的自身免疫。科学家们正在尝试使用 Treg 细胞来治疗自身免疫性疾病，例如系统性红斑狼疮。 目的：我们的目标是使用短链脂肪酸丁酸钠等刺激物，在体外从 C57 小鼠脾脏中分离的幼稚 CD4+T 细胞诱导 Foxp3+CD4+ T 细胞。此外，通过观察诱导后的Treg细胞中Foxp3、Ezh2（Enhancer of Zeste Homolog 2）和磷酸化Ezh2的变化，探讨Foxp3+ T细胞诱导与表观遗传修饰之间的关系。 材料与方法：采用免疫磁珠分离法从C57小鼠脾脏中分离初始CD4+ T细胞。加入适当浓度的抗CD28、抗CD3、IL-2、TGF-β1和丁酸钠诱导Foxp3表达72小时。然后，我们观察了 GSK126（Ezh2 抑制剂）在相同的 72 小时持续时间内对诱导的影响。然后，使用western blot和Q-PCR观察Foxp3、Ezh2和磷酸化Ezh2基因/蛋白表达的变化。结果：根据我们的结果，接受完全刺激的第3组的Foxp3和Ezh2表达水平显着较高（p
Context: CD4+CD25+ regulatory T (Treg) lymphocytes are critical for immune homeostasis. Foxp3 (Forkhead Box protein P3) is always considered as a marker of function and identities determination of Treg cells because of special occurring in Treg cell. People who lack Treg cells or have a low expression of Foxp3 gene will suffer fatal autoimmunity. Scientists are trying to use Treg cells as a treatment for autoimmune disease, such as systemic lupus erythematosus.Objective: Our objective was to induce Foxp3+CD4+ T cells from naive CD4+T cells isolated from C57 mice spleen in vitro using stimuli that include the short chain fatty acid sodium butyrate. Furthermore, to explore the relationship between Foxp3+ T cells induction and epigenetic modification, by observing the changes of Foxp3, Ezh2 (Enhancer of Zeste Homolog 2) and phosphorylated Ezh2 in the induced Treg cells.Materials and methods: The naive CD4+ T cells were separated from C57 mice spleen by immunomagnetic separation. Anti-CD28, anti-CD3, IL-2, TGF-beta 1, and sodium butyrate were added with proper concentration to induce Foxp3 expression during 72hours. Then, we observed the effect of GSK126 (Ezh2 inhibitor) on the induction within the same over 72hours duration. Then, western blot and Q-PCR were used to see the changes in gene/protein expression of Foxp3, Ezh2, and phosphorylated Ezh2.Results: According to our results, group 3 that received full stimulus had a significant higher level of Foxp3 and Ezh2 expression (p