The zinc finger transcription factor Zbtb7b represses CD8-lineage gene expression in peripheral CD4+ T cells.

The zinc finger transcription factor Zbtb7b represses CD8-lineage gene expression in peripheral CD4+ T cells.
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DOI:
10.1016/j.immuni.2008.09.019
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发表时间:
2008-12-19
期刊:
影响因子:
32.4
通讯作者:
Bosselut R
Bosselut R
中科院分区:
医学1区
文献类型:
--
作者:
Wang L;Wildt KF;Castro E;Xiong Y;Feigenbaum L;Tessarollo L;Bosselut R

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CD 4-CD 8在成熟T细胞中的表达是如何维持的,在很大程度上是未知的。本研究已经检查了锌指蛋白Zbtb 7 b,一个关键因素的承诺的MHC II限制性胸腺细胞的CD 4谱系,仍然在成熟的CD 4细胞中表达的锌指蛋白Zbtb 7 b在这个过程中的作用。我们发现Zbtb 7 B在外周血CD 4细胞中抑制CD 8谱系基因表达,包括CD 8和细胞毒性效应基因穿孔素和颗粒酶B的表达,并且对于效应分化期间IFNγ的适当抑制是重要的。Zbtb 7 b缺陷型CD 4细胞IFNγ的不适当表达需要Eomesodermin和Runx 3转录因子的活性。颗粒酶B表达需要Runx活性,表明Runx蛋白控制细胞毒性程序的表达。我们得出结论,Zbtb 7 b在成熟的CD 4 T细胞区室的一个关键功能是抑制CD 8谱系基因表达。
How CD4-CD8 expression is maintained in mature T cells is largely unknown. The present study has examined the role in this process of the zinc finger protein Zbtb7b, a critical factor for the commitment of MHC II-restricted thymocytes to the CD4 lineage, that remains expressed in mature CD4 cells. We show that Zbtb7b acts in peripheral CD4 cells to suppress CD8-lineage gene expression, including that of CD8 and cytotoxic effector genes perforin and Granzyme B, and is important for the proper repression of IFNγ during effector differentiation. The inappropriate expression of IFNγ by Zbtb7b-deficient CD4 cells required the activities of Eomesodermin and Runx3 transcription factors. Runx activity was needed for Granzyme B expression, indicating that Runx proteins control expression of the cytotoxic program. We conclude that a key function of Zbtb7b in the mature CD4 T cell compartment is to repress CD8-lineage gene expression.
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