Differential requirement of PKC-theta in the development and function of natural regulatory T cells.
Differential requirement of PKC-theta in the development and function of natural regulatory T cells.
复制标题
DOI：
10.1016/j.molimm.2008.08.275
复制
发表时间：
2008-12
影响因子：
3.6
通讯作者：
Sun, Zuoming
中科院分区：
文献类型：
--
作者：
Gupta, Sonal;Manicassamy, Santhakumar;Vasu, Chenthamarakshan;Kumar, Anvita;Shang, Weirong;Sun, Zuoming
CD4+CD25+ natural Treg cells, which are developed in the thymus, migrate to the periphery to actively maintain self-tolerance. Similar to conventional T cells, TCR signals are critical for the development and activation of Treg cell inhibitory function. While PKC-θ-mediated TCR signals are required for the activation of peripheral naïve T cells, they are dispensable for their thymic development. Here, we show that mice deficient in PKC-θ had a greatly reduced number of CD4+Foxp3+ Treg cells, which was independent of PKC-θ-regulated survival, as transgenic Bcl-xL could not restore the Treg cell population in PKC-θ−/− mice. Active and WT PKC-θ markedly stimulated, whereas inactive PKC-θ and dominant negative NFAT inhibited Foxp3 promoter activity. In addition, mice-deficient in calcineurin Aβ had a decreased Treg cell population, similar to that observed in PKC-θ deficient mice. It is likely that PKC-θ promoted the development of Treg cells by enhancing Foxp3 expression via activation of the calcineurin/NFAT pathway. Finally, Treg cells deficient in PKC-θ were as potent as WT Treg cells in inhibiting T cell activation, indicating that PKC-θ was not required for Treg cell-mediated inhibitory function. Our data highlight the contrasting roles PKC-θ plays in conventional T cell and natural Treg cell function.
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：
5.6
作者：
Manicassamy, S;Sadim, M;Sun, ZM
通讯作者：
Sun, ZM
影响因子：
5.3
作者：
Lin, X;O'Mahony, A;Greene, WC
通讯作者：
Greene, WC
影响因子：
4.4
作者：
Manicassainy, Santhakumar;Sun, Zuoming
通讯作者：
Sun, Zuoming
影响因子：
56.9
作者：
Hori, S;Nomura, T;Sakaguchi, S
通讯作者：
Sakaguchi, S