BCL6公司
生发中心
生物
关贸总协定3
细胞分化
CXCR5型
转录因子
细胞生物学
表观遗传学
抑制因子
B细胞
增强子
T细胞
免疫学
基因
抗体
遗传学
免疫系统
作者
Christine Nguyen,Matthew R. Kudek,Ryan Zander,Hongshen Niu,Jian Shen,Ashley M. Bauer,Donia Alson,Achia Khatun,Yao Chen,Jie Sun,William R. Drobyski,Brian T. Edelson,Weiguo Cui
出处
期刊:Journal of Immunology
[The American Association of Immunologists]
日期:2024-04-15
卷期号:212 (11): 1829-1842
标识
DOI:10.4049/jimmunol.2300355
摘要
In response to acute infection, naive CD4+ T cells primarily differentiate into T helper 1 (Th1) or T follicular helper (Tfh) cells that play critical roles in orchestrating cellular or humoral arms of immunity, respectively. However, despite the well established role of T-bet and BCL-6 in driving Th1 and Tfh cell lineage commitment, respectively, whether additional transcriptional circuits also underlie the fate bifurcation of Th1 and Tfh cell subsets is not fully understood. In this article, we study how the transcriptional regulator Bhlhe40 dictates the Th1/Tfh differentiation axis in mice. CD4+ T cell-specific deletion of Bhlhe40 abrogates Th1 but augments Tfh differentiation. We also assessed an increase in germinal center B cells and Ab production, suggesting that deletion of Bhlhe40 in CD4+ T cells not only alters Tfh differentiation but also their capacity to provide help to B cells. To identify molecular mechanisms by which Bhlhe40 regulates Th1 versus Tfh lineage choice, we first performed epigenetic profiling in the virus specific Th1 and Tfh cells following LCMV infection, which revealed distinct promoter and enhancer activities between the two helper cell lineages. Furthermore, we identified that Bhlhe40 directly binds to cis-regulatory elements of Th1-related genes such as Tbx21 and Cxcr6 to activate their expression while simultaneously binding to regions of Tfh-related genes such as Bcl6 and Cxcr5 to repress their expression. Collectively, our data suggest that Bhlhe40 functions as a transcription activator to promote Th1 cell differentiation and a transcription repressor to suppress Tfh cell differentiation.
科研通智能强力驱动
Strongly Powered by AbleSci AI