Overexpression of the Runx3 transcription factor increases the proportion of mature thymocytes of the CD8 single-positive lineage
Overexpression of the Runx3 transcription factor increases the proportion of mature thymocytes of the CD8 single-positive lineage
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DOI：
10.4049/jimmunol.174.5.2627
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发表时间：
2005-03-01
影响因子：
4.4
通讯作者：
Satake, M
中科院分区：
文献类型：
--
作者：
Kohu, K;Sato, T;Satake, M
Runx家族的转录因子被认为调节胸腺细胞的分化。Runx 3蛋白主要在T淋巴细胞的CD 4（-）8（+）亚群中检测到。在Runx 3缺陷小鼠的胸腺中，CD 4表达被去抑制，CD 4（-）8（+）胸腺细胞不发育。这清楚地表明Runx 3在CD 4沉默中起作用，但不一定证明它在CD 4（-）8（+）胸腺细胞本身的分化中起作用。在本研究中，我们创建了过表达Runx 3的转基因小鼠，并分析了这些动物中胸腺细胞的发育。在Runx 3转基因胸腺中，CD 4（-）8（+）细胞数量显著增加，而CD 4（+）8（+）和CD 4（+）8（-）细胞数量减少。CD 4（-）8（+）转基因胸腺细胞含有具有TCR（高）HSA（低）表型的成熟细胞。这些细胞从胸腺中释放，导致脾脏中CD 4（-）8（+）细胞水平相对于CD 4（+）8（-）细胞升高。Runx 3过表达还增加了II类限制性转基因TCR小鼠和I类缺陷背景小鼠中成熟CD 4（-）8（+）胸腺细胞的数量，这两种情况都有利于CD 4（+）8（-）谱系选择。因此，Runx 3可以驱动胸腺细胞选择CD 4（-）8（+）谱系。这种活性可能不仅仅是由于CD 4基因表达的简单沉默。
The Runx family of transcription factors is thought to regulate the differentiation of thymocytes. Runx3 protein is detected mainly in the CD4(-)8(+) subset of T lymphocytes. In the thymus of Runx3-deficient mice, CD4 expression is de-repressed and CD4(-)8(+) thymocytes do not develop. This clearly implicates Runx3 in CD4 silencing, but does not necessarily prove its role in the differentiation of CD4(-)8(+) thymocytes per se. In the present study, we created transgenic mice that overexpress Runx3 and analyzed the development of thymocytes in these animals. In the Runx3-transgenic thymus, the number of CD4(-)8(+) cells was greatly increased, whereas the numbers of CD4(+)8(+) and CD4(+)8(-) cells were reduced. The CD4(-)8(+) transgenic thymocytes contained mature cells with a TCR(high)HSA(low) phenotype. These cells were released from the thymus and contributed to the elevated level of CD4(-)8(+) cells relative to CD4(+)8(-) cells in the spleen. Runx3 overexpression also increased the number of mature CD4(-)8(+) thymocytes in mice with class II-restricted, transgenic TCR and in mice with a class I-deficient background, both of which are favorable for CD4(+)8(-) lineage selection. Thus, Runx3 can drive thymocytes to select the CD4(-)8(+) lineage. This activity is likely to be due to more than a simple silencing of CD4 gene expression.