PD-L1 regulates the development, maintenance, and function of induced regulatory T cells.
PD-L1 regulates the development, maintenance, and function of induced regulatory T cells.
复制标题
DOI：
10.1084/jem.20090847
复制
发表时间：
2009-12-21
期刊：
影响因子：
--
通讯作者：
Sharpe AH
中科院分区：
文献类型：
--
作者：
Francisco LM;Salinas VH;Brown KE;Vanguri VK;Freeman GJ;Kuchroo VK;Sharpe AH
程序性死亡（PD） 1 - PD配体（PD- l）途径和调节性T细胞（T reg）都有助于外周耐受性的维持。我们证明了PD-L1在调节诱导的T regg （iT regg）细胞发育和维持iT regg细胞功能方面具有关键作用。PD-L1−/−抗原提呈细胞能最小限度地将初始CD4 T细胞转化为iT reg细胞，表明PD-L1在iT reg细胞诱导中的重要作用。PD-L1包被微球在体外诱导iT reg细胞，表明PD-L1本身调控iT reg细胞的发育。此外，PD-L1增强和维持Foxp3的表达和iT regg细胞的抑制功能。PD-L1在体内控制iT reg细胞发育和功能方面的必要作用，可以通过在初始CD4 T细胞的PD-L1 - / - PD-L2 - / - Rag - / -受体中iT reg细胞转化的显着减少和致命炎症表型的快速发作来说明。PD-L1 iT reg细胞的发育是通过磷酸化akt、mTOR、S6和ERK2的下调以及PTEN的上调介导的，这些都是iT reg细胞发育的关键信号分子。因此，PD-L1可以通过促进iT reg细胞的诱导和维持来抑制T细胞的反应。这些研究定义了iT reg细胞发育和功能的新机制，以及控制T reg细胞可塑性的新策略。
Both the programmed death (PD) 1–PD-ligand (PD-L) pathway and regulatory T (T reg) cells are instrumental to the maintenance of peripheral tolerance. We demonstrate that PD-L1 has a pivotal role in regulating induced T reg (iT reg) cell development and sustaining iT reg cell function. PD-L1−/− antigen-presenting cells minimally convert naive CD4 T cells to iT reg cells, showing the essential role of PD-L1 for iT reg cell induction. PD-L1–coated beads induce iT reg cells in vitro, indicating that PD-L1 itself regulates iT reg cell development. Furthermore, PD-L1 enhances and sustains Foxp3 expression and the suppressive function of iT reg cells. The obligatory role for PD-L1 in controlling iT reg cell development and function in vivo is illustrated by a marked reduction in iT reg cell conversion and rapid onset of a fatal inflammatory phenotype in PD-L1−/−PD-L2−/− Rag−/− recipients of naive CD4 T cells. PD-L1 iT reg cell development is mediated through the down-regulation of phospho-Akt, mTOR, S6, and ERK2 and concomitant with the up-regulation of PTEN, all key signaling molecules which are critical for iT reg cell development. Thus, PD-L1 can inhibit T cell responses by promoting both the induction and maintenance of iT reg cells. These studies define a novel mechanism for iT reg cell development and function, as well as a new strategy for controlling T reg cell plasticity.
登录
查看更多内容
影响因子：
32.4
作者：
Fontenot, JD;Rasmussen, JP;Rudensky, AY
通讯作者：
Rudensky, AY
影响因子：
8.8
作者：
Bloom, D. D.;Chang, Z.;Knechtle, S. J.
通讯作者：
Knechtle, S. J.
影响因子：
3.1
作者：
Beswick, Ellen J.;Pinchuk, Irina V.;Reyes, Victor E.
通讯作者：
Reyes, Victor E.
影响因子：
8.8
作者：
Gao, W.;Lu, Y.;Strom, T. B.
通讯作者：
Strom, T. B.
影响因子：
64.8
作者：
Gavin, Marc A.;Rasmussen, Jeffrey P.;Rudensky, Alexander Y.
通讯作者：
Rudensky, Alexander Y.