Androgen receptor modulates Foxp3 expression in CD4+CD25+Foxp3+ regulatory T-cells.
Androgen receptor modulates Foxp3 expression in CD4+CD25+Foxp3+ regulatory T-cells.
复制标题
DOI：
10.1091/mbc.e14-08-1323
复制
发表时间：
2015-08-01
影响因子：
3.3
通讯作者：
Fijak M
中科院分区：
文献类型：
--
作者：
Walecki M;Eisel F;Klug J;Baal N;Paradowska-Dogan A;Wahle E;Hackstein H;Meinhardt A;Fijak M
CD 4 + CD 25 + Foxp 3 + Treg细胞对于维持免疫稳态至关重要。雄激素在人体中显著诱导Foxp 3表达并调节Treg细胞的分化。一个功能性雄激素受体结合位点被确定在Foxp 3基因座内，导致组蛋白H4的表观遗传变化。CD 4 + CD 25 + Foxp 3+调节性T（Treg）细胞能够抑制效应T细胞中的增殖和细胞因子产生，并且在免疫应答和预防自身免疫性疾病中发挥主要作用。Treg细胞发育和功能的主要调节因子是转录因子Foxp 3。已知几种细胞因子如TGF-β和IL-2调节Foxp 3表达以及Foxp 3基因座的甲基化。我们先前证明，睾酮治疗诱导体内和体外Treg细胞群的强烈增加。因此，我们试图研究雄激素对Foxp 3表达和调节的直接影响。我们显示了一个显着的雄激素依赖性增加的Foxp 3表达在人类T细胞的妇女在排卵期的月经周期，但不是从男性，并确定一个功能性雄激素反应元件内的Foxp 3基因座。雄激素受体的结合导致组蛋白H4乙酰化状态的变化，而Foxp 3基因中确定的CpG区域的甲基化不受影响。我们的研究结果为雄激素在Treg细胞分化中的调节作用提供了新的证据。
CD4+CD25+Foxp3+ Treg cells are crucial for the maintenance of immunological homeostasis. Androgens significantly induce Foxp3 expression in humans and regulate the differentiation of Treg cells. A functional androgen receptor–binding site is identified within the Foxp3 locus leading to epigenetic changes of histone H4. CD4+CD25+Foxp3+ regulatory T (Treg) cells are able to inhibit proliferation and cytokine production in effector T-cells and play a major role in immune responses and prevention of autoimmune disease. A master regulator of Treg cell development and function is the transcription factor Foxp3. Several cytokines, such as TGF-β and IL-2, are known to regulate Foxp3 expression as well as methylation of the Foxp3 locus. We demonstrated previously that testosterone treatment induces a strong increase in the Treg cell population both in vivo and in vitro. Therefore we sought to investigate the direct effect of androgens on expression and regulation of Foxp3. We show a significant androgen-dependent increase of Foxp3 expression in human T-cells from women in the ovulatory phase of the menstrual cycle but not from men and identify a functional androgen response element within the Foxp3 locus. Binding of androgen receptor leads to changes in the acetylation status of histone H4, whereas methylation of defined CpG regions in the Foxp3 gene is unaffected. Our results provide novel evidence for a modulatory role of androgens in the differentiation of Treg cells.