Runx3 and Runx1 are required for CD8 T cell development during thymopoiesis

被引:325
作者
Woolf, E
Xiao, CY
Fainaru, O
Lotem, J
Rosen, D
Negreanu, V
Bernstein, Y
Goldenberg, D
Brenner, O
Berke, G
Levanon, D
Groner, Y [1 ]
机构
[1] Weizmann Inst Sci, Dept Mol Genet, IL-76100 Rehovot, Israel
[2] Weizmann Inst Sci, Dept Immunol, IL-76100 Rehovot, Israel
[3] Weizmann Inst Sci, Dept Vet Resources, IL-76100 Rehovot, Israel
关键词
D O I
10.1073/pnas.1232420100
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
The RUNX transcription factors are important regulators of lineage-specific gene expression. RUNX are bifunctional, acting both as activators and repressors of tissue-specific target genes. Recently, we have demonstrated that Runx3 is a neurogenic transcription factor, which regulates development and survival of proprioceptive neurons in dorsal root ganglia. Here we report that Runx3 and Runx1 are highly expressed in thymic medulla and cortex, respectively, and function in development of CD8 T cells during thymopoiesis. Runx3-deficient (Runx3 KO) mice display abnormalities in CD4 expression during lineage decisions and impairment of CD8 T cell maturation in the thymus. A large proportion of Runx3 KO peripheral CD8 T cells also expressed CD4, and in contrast to wild-type, their proliferation ability was largely reduced. In addition, the in vitro cytotoxic activity of alloimmunized peritoneal exudate lymphocytes was significantly lower in Runx3 KO compared with T mice. In a compound mutant mouse, null for Runx3 and heterozygous for Runx1 (Runx3(-/-);Runx1(+/-)), all peripheral CD8 T cells also expressed CD4, resulting in a complete lack of single-positive CD8(+) T cells in the spleen. The results provide information on the role of Runx3 and Runx1 in thymopoiesis and suggest that both act as transcriptional repressors of CD4 expression during T cell lineage decisions.
引用
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页码:7731 / 7736
页数:6
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