An oscillatory switch in mTOR kinase activity sets regulatory T cell responsiveness.
An oscillatory switch in mTOR kinase activity sets regulatory T cell responsiveness.
复制标题
DOI：
10.1016/j.immuni.2010.11.024
复制
发表时间：
2010-12-14
期刊：
影响因子：
32.4
通讯作者：
Matarese G
中科院分区：
文献类型：
--
作者：
Procaccini C;De Rosa V;Galgani M;Abanni L;Calì G;Porcellini A;Carbone F;Fontana S;Horvath TL;La Cava A;Matarese G
CD4+CD25hiFoxP3+调节性T细胞(Treg)的体外无能状态与其体内增殖能力存在差异。这一悖论的潜在机制尚不清楚。在这里，我们发现Treg细胞的无能状态依赖于瘦素诱导的哺乳动物靶标雷帕霉素(MTOR)途径的活性增加：在T细胞受体(TCR)刺激之前，用雷帕霉素短暂抑制mTOR，使Treg细胞在没有外源白介素2(IL-2)的情况下高度增殖。这是一种动态和振荡的现象，其特征是瘦素-mTOR途径早期下调，随后mTOR激活增加，这是Treg细胞扩张所必需的。这些数据表明，能量代谢通过瘦素-mTOR轴，设定了Treg细胞的反应性，利用这些信息来控制免疫耐受和自身免疫。
There is a discrepancy between the in vitro anergic state of CD4+CD25hiFoxP3+ regulatory T (Treg) cells and their in vivo proliferative capability. The underlying mechanism of this paradox is unknown. Here we show that the anergic state of Treg cells depends on the elevated activity of the mammalian target of rapamycin-(mTOR)-pathway induced by leptin: a transient inhibition of mTOR with rapamycin, before T-cell-receptor-(TCR)-stimulation, made Treg cells highly proliferative in the absence of exogenous interleukin-2 (IL-2). This was a dynamic and oscillatory phenomenon characterized by an early downregulation of the leptin-mTOR-pathway followed by an increase in mTOR activation necessary for Treg cell expansion to occur. These data suggest that energy metabolism, through the leptin-mTOR-axis, sets responsiveness of Treg cells that use this information to control immune tolerance and autoimmunity.