Deutsches Rheuma-Forschungszentrum Berlin, Berlin, Germany.
Nat Immunol. 2010 Nov;11(11):1057-62. doi: 10.1038/ni.1945. Epub 2010 Oct 10.
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.
辅助性 T 淋巴细胞被抗原激活后，从静息状态切换到克隆扩增。这种转换需要转录因子 Foxo1 的失活，Foxo1 是静息辅助性 T 淋巴细胞中表达的增殖抑制剂。在扩增的早期抗原依赖性阶段，Foxo1 通过抗原受体介导的翻译后修饰失活。在这里，我们表明在扩增的晚期，Foxo1 不再受到翻译后调控，而是被白细胞介素 2（IL-2）诱导的 microRNA miR-182 转录后抑制。在辅助性 T 淋巴细胞中特异性抑制 miR-182 限制了它们在体外和体内的群体扩增。我们的研究结果表明 miR-182 在生理调节 IL-2 驱动的辅助性 T 细胞介导的免疫反应中起着核心作用，并为新的治疗可能性开辟了道路。
