TY - JOUR
T1 - Overexpression of the Runx3 transcription factor increases the proportion of mature thymocytes of the CD8 single-positive lineage
AU - Kohu, Kazuyoshi
AU - Sato, Takehito
AU - Ohno, Shin Ichiro
AU - Hayashi, Keitaro
AU - Uchino, Ryuji
AU - Abe, Natsuma
AU - Nakazato, Megumi
AU - Yoshida, Naomi
AU - Kikuchi, Toshiaki
AU - Iwakura, Yoichiro
AU - Inoue, Yoshihiro
AU - Watanabe, Toshio
AU - Habu, Sonoko
AU - Satake, Masanobu
PY - 2005/3/1
Y1 - 2005/3/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=20044383185&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=20044383185&partnerID=8YFLogxK
U2 - 10.4049/jimmunol.174.5.2627
DO - 10.4049/jimmunol.174.5.2627
M3 - Article
C2 - 15728469
AN - SCOPUS:20044383185
VL - 174
SP - 2627
EP - 2636
JO - Journal of Immunology
JF - Journal of Immunology
SN - 0022-1767
IS - 5
ER -