Overexpression of the Runx3 transcription factor increases the proportion of mature thymocytes of the CD8 single-positive lineage.

نویسندگان

  • Kazuyoshi Kohu
  • Takehito Sato
  • Shin-Ichiro Ohno
  • Keitaro Hayashi
  • Ryuji Uchino
  • Natsumi Abe
  • Megumi Nakazato
  • Naomi Yoshida
  • Toshiaki Kikuchi
  • Yoichiro Iwakura
  • Yoshihiro Inoue
  • Toshio Watanabe
  • Sonoko Habu
  • Masanobu Satake
چکیده

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.

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عنوان ژورنال:
  • Journal of immunology

دوره 174 5  شماره 

صفحات  -

تاریخ انتشار 2005