Glycogen synthase kinase-3 controls IL-10 expression in CD4(+) effector T-cell subsets through epigenetic modification of the IL-10 promoter.
Glycogen synthase kinase-3 controls IL-10 expression in CD4(+) effector T-cell subsets through epigenetic modification of the IL-10 promoter.
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糖原合成酶激酶 3 通过 IL-10 启动子的表观遗传修饰控制 CD4(+) 效应 T 细胞亚群中 IL-10 的表达。
DOI：
10.1002/eji.201444661
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发表时间：
2015-04
影响因子：
5.4
通讯作者：
Wraith, David C.
中科院分区：
文献类型：
--
作者：
Hill, Elaine V.;Ng, T. H. Sky;Burton, Bronwen R.;Oakley, Charly M.;Malik, Karim;Wraith, David C.
丝氨酸/苏氨酸激酶糖原合成酶激酶-3（GSK 3）在平衡促炎细胞因子和抗炎细胞因子中起重要作用。我们研究了GSK 3在CD 4 + T辅助细胞亚群产生IL-10中的作用。用GSK 3抑制剂处理幼稚鼠CD 4 + T细胞不影响其IL-10的产生。然而，用GSK 3抑制剂处理Th 1和Th 2细胞显著增加IL-10的产生。GSK 3抑制还导致从人血液中分离的Th 1、Th 2和Th 17亚群中IL-10的上调。通过IL-10依赖性机制，在过继转移实验中，GSK 3抑制剂处理的小鼠Th 1细胞的致脑炎潜力显著降低。对小鼠IL-10启动子响应于抑制Th 1细胞中的GSK 3的分析显示，组蛋白H3乙酰化和甲基化的变化指示了转录活性状态的改变。此外，GSK 3抑制增加了转录因子c-Maf、Nfil 3和GATA 3的表达，与IL-10的增加相关。这些发现在自身免疫性疾病的背景下很重要，因为它们表明可以通过GSK 3抑制来重新编程致病细胞。
The serine/threonine kinase glycogen synthase kinase-3 (GSK3) plays an important role in balancing pro- and anti-inflammatory cytokines. We have examined the role of GSK3 in production of IL-10 by subsets of CD4+ T helper cells. Treatment of naive murine CD4+ T cells with GSK3 inhibitors did not affect their production of IL-10. However, treatment of Th1 and Th2 cells with GSK3 inhibitors dramatically increased production of IL-10. GSK3 inhibition also led to upregulation of IL-10 among Th1, Th2, and Th17 subsets isolated from human blood. The encephalitogenic potential of GSK3 inhibitor treated murine Th1 cells was significantly reduced in adoptive transfer experiments by an IL-10-dependent mechanism. Analysis of the murine IL-10 promoter in response to inhibition of GSK3 in Th1 cells showed modification to a transcriptionally active state indicated by changes in histone H3 acetylation and methylation. Additionally, GSK3 inhibition increased expression of the transcription factors c-Maf, Nfil3, and GATA3, correlating with the increase in IL-10. These findings are important in the context of autoimmune disease since they show that it is possible to reprogram disease-causing cells through GSK3 inhibition.
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DOI：
10.4049/jimmunol.181.1.338
发表时间：
2008-07-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
De Sarno P;Axtell RC;Raman C;Roth KA;Alessi DR;Jope RS
通讯作者：
Jope RS
影响因子：
64.5
作者：
Goldberg, Aaron D.;Allis, C. David;Bernstein, Emily
通讯作者：
Bernstein, Emily
DOI：
10.4049/jimmunol.1003511
发表时间：
2011-02-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Beurel E;Yeh WI;Michalek SM;Harrington LE;Jope RS
通讯作者：
Jope RS
影响因子：
5.4
作者：
Jutel, M;Akdis, M;Akdis, CA
通讯作者：
Akdis, CA
影响因子：
14.2
作者：
Francis, JN;Till, SJ;Durham, SR
通讯作者：
Durham, SR