The role of the Runx transcription factors in thymocyte differentiation and in homeostasis of naive T cells.
The role of the Runx transcription factors in thymocyte differentiation and in homeostasis of naive T cells.
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DOI：
10.1084/jem.20070133
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发表时间：
2007-08-06
期刊：
影响因子：
--
通讯作者：
Littman DR
中科院分区：
文献类型：
--
作者：
Egawa T;Tillman RE;Naoe Y;Taniuchi I;Littman DR
Runx 转录调节因子家族的成员对于在 T 细胞发育的不同阶段适当表达 CD4 和 CD8 是必需的。这些因子在 T 细胞发育其他方面的作用尚不清楚。我们采用了一种策略，在胸腺细胞发育的不同阶段有条件地灭活编码Runx1或Runx3的基因，证明Runx1调节发育中的胸腺细胞从CD4−CD8−双阴性阶段到CD4+CD8+双阳性(DP)阶段以及从DP阶段到成熟单阳性阶段的转变。 Runx1 和 Runx3 缺陷分别导致成熟胸腺细胞和 CD4+ 辅助 T 细胞和 CD8+ 细胞毒性 T 细胞谱系的显着减少。 Runx1 缺陷型 CD4+ T 细胞的白细胞介素 7 受体表达显着降低，且存活时间较短。此外，Runx1 和 Runx3 在 DP 阶段的失活导致 CD8+ 成熟胸腺细胞的发育严重受阻。这些结果表明 Runx 蛋白在 T 细胞发育的多个阶段以及成熟 T 细胞的稳态中发挥重要作用。
Members of the Runx family of transcriptional regulators are required for the appropriate expression of CD4 and CD8 at discrete stages of T cell development. The roles of these factors in other aspects of T cell development are unknown. We used a strategy to conditionally inactivate the genes encoding Runx1 or Runx3 at different stages of thymocyte development, demonstrating that Runx1 regulates the transitions of developing thymocytes from the CD4−CD8− double-negative stage to the CD4+CD8+ double-positive (DP) stage and from the DP stage to the mature single-positive stage. Runx1 and Runx3 deficiencies caused marked reductions in mature thymocytes and T cells of the CD4+ helper and CD8+ cytotoxic T cell lineages, respectively. Runx1-deficient CD4+ T cells had markedly reduced expression of the interleukin 7 receptor and exhibited shorter survival. In addition, inactivation of both Runx1 and Runx3 at the DP stages resulted in a severe block in development of CD8+ mature thymocytes. These results indicate that Runx proteins have important roles at multiple stages of T cell development and in the homeostasis of mature T cells.
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