p27(Kip1) negatively regulates the magnitude and persistence of CD4 T cell memory.
p27(Kip1) negatively regulates the magnitude and persistence of CD4 T cell memory.
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DOI：
10.4049/jimmunol.1201482
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发表时间：
2012-12-01
期刊：
影响因子：
--
通讯作者：
Suresh M
中科院分区：
文献类型：
--
作者：
Jatzek A;Tejera MM;Singh A;Sullivan JA;Plisch EH;Suresh M
我们对naïve T细胞分化为不同的效应细胞谱系了解甚多，但CD4 T细胞记忆产生和维持的分子机制尚不清楚。我们的研究将细胞周期调节因子p27Kip1作为TH1 CD4 T细胞记忆的建立和长期维持的重要负调节因子赋予了新的作用。我们证明p27Kip1可能通过增加效应CD4 T细胞中的T-bet: Bcl-6比率来限制记忆前体的分化和存活。p27Kip1通过至少部分是T细胞固有的机制促进效应CD4 T细胞的凋亡和收缩，显著限制记忆性CD4 T细胞的丰度。此外，我们将p27kip1依赖性细胞凋亡与CD4 T细胞记忆的衰退联系起来，可能是通过抑制γ链受体的表达和Wnt/β-catenin信号通路的下游效应物tgf -1。我们通过表明p27Kip1对CD4 T细胞记忆的拮抗作用需要其周期蛋白依赖的激酶结合域来扩展这些发现。总的来说，这些发现为外周CD4 T细胞稳态控制机制提供了关键见解，并确定p27Kip1是增强疫苗诱导的CD4 T细胞记忆的靶标。
Much is known about the differentiation of naïve T cells into distinct lineages of effector cells, but the molecular mechanisms underlying the generation and maintenance of CD4 T cell memory are poorly characterized. Our studies ascribe a novel role for the cell cycle regulator p27Kip1, as a prominent negative regulator of the establishment and long-term maintenance of TH1 CD4 T cell memory. We demonstrate that p27Kip1 might restrict the differentiation and survival of memory precursors by increasing the T-bet: Bcl-6 ratio in effector CD4 T cells. Promoting apoptosis and contraction of effector CD4 T cells by mechanisms that are at least in part T cell intrinsic, p27Kip1 markedly limits the abundance of memory CD4 T cells. Furthermore, we causally link p27Kip1-dependent apoptosis to the decay of CD4 T cell memory, possibly by repressing the expression of γ-chain receptors and the downstream effector of the Wnt/β-catenin signaling pathway, Tcf-1. We extend these findings by showing that the antagonistic effects of p27Kip1 on CD4 T cell memory requires its cyclin dependent kinase-binding domain. Collectively, these findings have provided key insights into the mechanisms underlying the governance of peripheral CD4 T cell homeostasis and identify p27Kip1 as a target to enhance vaccine-induced CD4 T cell memory.
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影响因子：
32.4
作者：
Marshall HD;Chandele A;Jung YW;Meng H;Poholek AC;Parish IA;Rutishauser R;Cui W;Kleinstein SH;Craft J;Kaech SM
通讯作者：
Kaech SM
影响因子：
30.5
作者：
Luethje, Katja;Kallies, Axel;Nutt, Stephen L.
通讯作者：
Nutt, Stephen L.
影响因子：
32.4
作者：
Choi YS;Kageyama R;Eto D;Escobar TC;Johnston RJ;Monticelli L;Lao C;Crotty S
通讯作者：
Crotty S
DOI：
10.1084/jem.20030735
发表时间：
2003-12-15
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Kondrack RM;Harbertson J;Tan JT;McBreen ME;Surh CD;Bradley LM
通讯作者：
Bradley LM
影响因子：
8
作者：
Pippa, R.;Espinosa, L.;Bachs, O.
通讯作者：
Bachs, O.