Department of Microbiology and Immunology, Keio University School of Medicine, Shinanomachi, Tokyo 160-8582, Japan.
Cell Rep. 2012 Apr 19;1(4):360-73. doi: 10.1016/j.celrep.2012.02.007. Epub 2012 Mar 29.
The PI3K-Akt-mTORC1 axis contributes to the activation, survival, and proliferation of CD4(+) T cells upon stimulation through TCR and CD28. Here, we demonstrate that the suppression of this axis by deletion of p85α or PI3K/mTORC1 inhibitors as well as T cell-specific deletion of raptor, an essential component of mTORC1, impairs Th17 differentiation in vitro and in vivo in a S6K1/2-dependent fashion. Inhibition of PI3K-Akt-mTORC1-S6K1 axis impairs the downregulation of Gfi1, a negative regulator of Th17 differentiation. Furthermore, we demonstrate that S6K2, a nuclear counterpart of S6K1, is induced by the PI3K-Akt-mTORC1 axis, binds RORγ, and carries RORγ to the nucleus. These results point toward a pivotal role of PI3K-Akt-mTORC1-S6K1/2 axis in Th17 differentiation.
PI3K-Akt-mTORC1 轴在 TCR 和 CD28 刺激后促进 CD4(+) T 细胞的激活、存活和增殖。在这里，我们证明通过敲除 p85α 或 PI3K/mTORC1 抑制剂以及 T 细胞特异性敲除 raptor（mTORC1 的必需成分）抑制该轴，以 S6K1/2 依赖的方式在体外和体内损害 Th17 分化。抑制 PI3K-Akt-mTORC1-S6K1 轴会损害 Th17 分化的负调控因子 Gfi1 的下调。此外，我们证明 S6K1 的核对应物 S6K2 被 PI3K-Akt-mTORC1 轴诱导，与 RORγ 结合，并将 RORγ 带到细胞核。这些结果表明 PI3K-Akt-mTORC1-S6K1/2 轴在 Th17 分化中起着关键作用。
