Aging is associated with increased regulatory T-cell function.
Aging is associated with increased regulatory T-cell function.
复制标题
DOI：
10.1111/acel.12191
复制
发表时间：
2014-06
期刊：
影响因子：
7.8
通讯作者：
Yung R
中科院分区：
文献类型：
--
作者：
Garg SK;Delaney C;Toubai T;Ghosh A;Reddy P;Banerjee R;Yung R
调节性T细胞(Treg，CD4+CD25+)功能障碍被认为在免疫衰老中起关键作用，并通过抑制T细胞反应而增加疾病的易感性。Foxp3是Treg功能的主要调节者，其表达受几个表观遗传不稳定的启动子和增强子的控制。这些区域内CpG位点的去甲基化与FoxP3表达增加和抑制表型的发展有关。我们检测了幼龄(3-4个月)和老年(18-20个月)C57BL/6小鼠FoxP3表达的差异。在老年小鼠中，来自CD4+T细胞的DNA发生了低甲基化，这也表现出Treg数量和FoxP3表达的增加。此外，老年小鼠的Treg在体外也比年轻小鼠的Treg具有更强的抑制效应T细胞(Tef)增殖的能力。在与DC共培养的过程中，老年小鼠的Tregs表现出更大的氧化还原重塑介导的抑制TJeff增殖的作用，因为它比年轻小鼠的Tregs更大程度地减少了细胞外半胱氨酸的可获得性，为TJeff的增殖创造了不利的环境。老年小鼠的Tregs产生更高的IL-10水平，并比年轻小鼠的Tregs更强烈地抑制DC上CD86的表达，这表明T细胞活性降低。综上所述，这些结果揭示了一种潜在的机制，即较高的Treg介导的活性可能有助于随着年龄的增长而增加免疫抑制。
Regulatory T-cell (Treg, CD4+CD25+) dysfunction is suspected to play a key role in immune senescence and contributes to increased susceptibility to diseases with age by suppressing T-cell responses. FoxP3 is a master regulator of Treg function, and its expression is under control of several epigenetically labile promoters and enhancers. Demethylation of CpG sites within these regions is associated with increased FoxP3 expression and development of a suppressive phenotype. We examined differences in FoxP3 expression between young (3–4 months) and aged (18–20 months) C57BL/6 mice. DNA from CD4+ T cells is hypomethylated in aged mice, which also exhibit increased Treg numbers and FoxP3 expression. Additionally, Treg from aged mice also have greater ability to suppress effector T-cell (Teff) proliferation in vitro than Tregs from young mice. Tregs from aged mice exhibit greater redox remodeling–mediated suppression of Teff proliferation during coculture with DCs by decreasing extracellular cysteine availability to a greater extent than Tregs from young mice, creating an adverse environment for Teff proliferation. Tregs from aged mice produce higher IL-10 levels and suppress CD86 expression on DCs more strongly than Tregs from young mice, suggesting decreased T-cell activity. Taken together, these results reveal a potential mechanism of higher Treg-mediated activity that may contribute to increased immune suppression with age.
登录
查看更多内容
影响因子：
4.3
作者：
Han, Guang-Ming;Zhao, Baohua;Feng, Ji-Ming
通讯作者：
Feng, Ji-Ming
影响因子：
4.4
作者：
Misra, N;Bayry, J;Kaveri, SV
通讯作者：
Kaveri, SV
影响因子：
30.5
作者：
Fallarino, F;Grohmann, U;Puccetti, P
通讯作者：
Puccetti, P
影响因子：
4.6
作者：
Gregg, R;Smith, CM;Moss, PA
通讯作者：
Moss, PA
影响因子：
100.3
作者：
Huehn, Jochen;Polansky, Julia K.;Hamann, Alf
通讯作者：
Hamann, Alf