Genome-wide Analysis Identifies Bcl6-Controlled Regulatory Networks during T Follicular Helper Cell Differentiation.
Genome-wide Analysis Identifies Bcl6-Controlled Regulatory Networks during T Follicular Helper Cell Differentiation.
复制标题
全基因组分析确定了T卵泡辅助细胞分化过程中Bcl6控制的调节网络。
DOI：
10.1016/j.celrep.2016.01.038
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发表时间：
2016-02-23
期刊：
影响因子：
8.8
通讯作者：
Dong C
中科院分区：
文献类型：
--
作者：
Liu X;Lu H;Chen T;Nallaparaju KC;Yan X;Tanaka S;Ichiyama K;Zhang X;Zhang L;Wen X;Tian Q;Bian XW;Jin W;Wei L;Dong C
滤泡辅助性T细胞（Tfh）是一种独特的T细胞亚群，具有促进体液免疫的功能. Bcl 6已被确定为Tfh细胞中的一个强制性转录因子;然而，Bcl 6功能的分子机制仍然在很大程度上未知。在这里，我们通过分析全基因组Bcl 6占有率和转录组谱来定义Tfh细胞中的Bcl 6靶基因。Tfh细胞中Bcl 6的结合与5-羟甲基胞嘧啶（5-hmC）的减少密切相关，与Th 9、B细胞和巨噬细胞中的共有序列不同。重要的是，Bcl 6通过拮抗IL-7 R（CD 127）/信号转导和转录激活因子（STAT）5轴促进Tfh细胞分化; T细胞中Bcl 6基因的缺失导致IL-7 R-STAT 5信号传导增强和CD 127 hi非Tfh细胞的大量扩增。因此，我们的研究系统地检查Bcl 6控制的调控网络，并提供了重要的见解，其在Tfh细胞的生物学功能。Liu等人研究了Bcl 6在Tfh细胞编程中的作用：Bcl 6与染色质的结合与5 hmC降低有关。Bcl 6至少部分通过拮抗IL-7 R/STAT 5轴来指导Tfh发育。
T follicular helper (Tfh) cell is a unique T cell subset specialized in promoting humoral immunity. Bcl6 has been identified as an obligatory transcription factor in Tfh cells; however, the molecular mechanism underlying Bcl6 function remains largely unknown. Here, we defined Bcl6 target genes in Tfh cells by analyzing genome-wide Bcl6 occupancy together with transcriptome profiling. With consensus sequences different from those in Th9, B cells and macrophages, Bcl6 binding in Tfh cell was closely associated with decrease in 5-hydroxymethylcytosine (5hmC). Importantly, Bcl6 promoted Tfh cell differentiation through antagonizing IL-7R (CD127)/signal transducer and activator of transcription (STAT) 5 axis; deletion of the Bcl6 gene in T cells results in enhanced IL-7R-STAT5 signaling and substantial expansion of CD127hi non-Tfh cells. Our study thus systemically examines Bcl6-controlled regulatory networks and provides important insights into its biological functions in Tfh cells. Liu et al. examine the roles of Bcl6 during Tfh cell programming: Bcl6 binding to chromatin is associated with decreased 5hmC. Bcl6 directs Tfh development, at least in part, through antagonizing the IL-7R/STAT5 axis.