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

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

Research output: Contribution to journalArticlepeer-review

64 Citations (Scopus)

Abstract

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 TCRhighHSAlow 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.

Original languageEnglish
Pages (from-to)2627-2636
Number of pages10
JournalJournal of Immunology
Volume174
Issue number5
DOIs
Publication statusPublished - 2005 Mar 1

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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