Transcription factor Foxp1 exerts essential cell-intrinsic regulation of the quiescence of naive T cells.
Transcription factor Foxp1 exerts essential cell-intrinsic regulation of the quiescence of naive T cells.
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T细胞静止背后的分子机制知之甚少。在这里，我们报告说，成熟的幼稚CD 8 + T细胞缺乏转录因子Foxp 1获得效应表型和功能，并直接增殖白细胞介素7（IL-7）在体外。Foxp 1通过拮抗Foxo 1抑制IL-7受体α链（IL-7 R α）的表达，并通过激酶MEK和Erk负调节信号传导。Foxp 1的急性缺失诱导幼稚T细胞获得效应表型并在淋巴细胞补充小鼠中增殖。Foxp 1缺陷的幼稚CD 8 + T细胞甚至在缺乏主要组织相容性复合物I类的淋巴细胞减少小鼠中增殖。我们的研究结果表明，Foxp 1发挥幼稚T细胞静止的基本细胞内在调节，提供了直接的证据表明，淋巴细胞静止是通过积极维护的机制，包括转录调控。
The molecular mechanisms that underlie T cell quiescence are poorly understood. Here we report that mature naive CD8+ T cells lacking the transcription factor Foxp1 gained effector phenotype and function and proliferated directly in response to interleukin 7 (IL-7) in vitro. Foxp1 repressed expression of the IL-7 receptor α-chain (IL-7Rα) by antagonizing Foxo1 and negatively regulated signaling by the kinases MEK and Erk. Acute deletion of Foxp1 induced naive T cells to gain an effector phenotype and proliferate in lymphoreplete mice. Foxp1-deficient naive CD8+ T cells proliferated even in lymphopenic mice deficient in major histocompatibility complex class I. Our results demonstrate that Foxp1 exerts essential cell-intrinsic regulation of naive T cell quiescence, providing direct evidence that lymphocyte quiescence is achieved through actively maintained mechanisms that include transcriptional regulation.