The microRNA miR-182 is induced by IL-2 and promotes clonal expansion of activated helper T lymphocytes
The microRNA miR-182 is induced by IL-2 and promotes clonal expansion of activated helper T lymphocytes
复制标题
DOI：
10.1038/ni.1945
复制
发表时间：
2010-11-01
影响因子：
30.5
通讯作者：
Mashreghi, Mir-Farzin
中科院分区：
文献类型：
--
作者：
Stittrich, Anna-Barbara;Haftmann, Claudia;Mashreghi, Mir-Farzin
被抗原激活后，辅助 T 淋巴细胞从静止状态转变为克隆扩张。这种转换需要转录因子 Foxo1 失活，Foxo1 是一种在静息辅助 T 淋巴细胞中表达的增殖抑制因子。在扩增的早期抗原依赖性阶段，Foxo1 被抗原受体介导的翻译后修饰失活。在这里，我们表明，在扩增的后期，Foxo1 不再受到翻译后调节，而是被白细胞介素 2 (IL-2) 诱导的 microRNA miR-182 抑制。辅助 T 淋巴细胞中 miR-182 的特异性抑制限制了其体外和体内群体扩张。我们的结果证明了 miR-182 在 IL-2 驱动的辅助 T 细胞介导的免疫反应的生理调节中发挥着核心作用，并开辟了新的治疗可能性。
After being activated by antigen, helper T lymphocytes switch from a resting state to clonal expansion. This switch requires inactivation of the transcription factor Foxo1, a suppressor of proliferation expressed in resting helper T lymphocytes. In the early antigen-dependent phase of expansion, Foxo1 is inactivated by antigen receptor-mediated post-translational modifications. Here we show that in the late phase of expansion, Foxo1 was no longer post-translationally regulated but was inhibited post-transcriptionally by the interleukin 2 (IL-2)-induced microRNA miR-182. Specific inhibition of miR-182 in helper T lymphocytes limited their population expansion in vitro and in vivo. Our results demonstrate a central role for miR-182 in the physiological regulation of IL-2-driven helper T cell-mediated immune responses and open new therapeutic possibilities.