Setoguchi Ruka, Tachibana Masashi, Naoe Yoshinori, Muroi Sawako, Akiyama Kaori, Tezuka Chieko, Okuda Tsukasa, Taniuchi Ichiro
Laboratory for Transcriptional Regulation, RIKEN Research Center for Allergy and Immunology, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama 230-0045, Japan.
Science. 2008 Feb 8;319(5864):822-5. doi: 10.1126/science.1151844.
Mouse CD4+CD8+ double-positive (DP) thymocytes differentiate into CD4+ helper-lineage cells upon expression of the transcription factor Th-POK but commit to the CD8+ cytotoxic lineage in its absence. We report the redirected differentiation of class I-restricted thymocytes into CD4+CD8- helper-like T cells upon loss of Runx transcription factor complexes. A Runx-binding sequence within the Th-POK locus acts as a transcriptional silencer that is essential for Th-POK repression and for development of CD8+ T cells. Thus, Th-POK expression and genetic programming for T helper cell development are actively inhibited by Runx-dependent silencer activity, allowing for cytotoxic T cell differentiation. Identification of the transcription factors network in CD4 and CD8 lineage choice provides insight into how distinct T cell subsets are developed for regulating the adaptive immune system.
小鼠CD4⁺CD8⁺双阳性（DP）胸腺细胞在转录因子Th-POK表达时分化为CD4⁺辅助谱系细胞，但在缺乏Th-POK时则定向分化为CD8⁺细胞毒性谱系。我们报告了在Runx转录因子复合物缺失时，I类限制性胸腺细胞重定向分化为CD4⁺CD8⁻辅助样T细胞。Th-POK基因座内的一个Runx结合序列作为转录沉默子，对于Th-POK的抑制以及CD8⁺T细胞的发育至关重要。因此Runx依赖的沉默子活性积极抑制Th-POK的表达和T辅助细胞发育的基因编程，从而允许细胞毒性T细胞分化。CD4和CD8谱系选择中转录因子网络的鉴定为不同T细胞亚群如何发育以调节适应性免疫系统提供了见解。
