The histone methyltransferase EZH2 primes the early differentiation of follicular helper T cells during acute viral infection.
Xiangyu ChenGuoshuai CaoJialin WuXinxin WangZhiwei PanJianbao GaoQin TianLifan XuZhirong LiYaxing HaoQizhao HuangPengcheng WangMinglu XiaoLuoyingzi XieShupei TangZhenyu LiuLi HuJianfang TangRan HeLi WangXinyuan ZhouYuzhang WuMengjie ChenBeicheng SunBo ZhuJun HuangLilin YePublished in: Cellular & molecular immunology (2019)
Epigenetic modifications to histones dictate the differentiation of naïve CD4+ T cells into different subsets of effector T helper (TH) cells. The histone methyltransferase enhancer of zeste homolog 2 (EZH2) has been implicated in the mechanism regulating the differentiation of TH1, TH2 and regulatory T (Treg) cells. However, whether and how EZH2 regulates follicular helper T (TFH) cell differentiation remain unknown. Using a mouse model of acute lymphocytic choriomeningitis virus (LCMV) infection, we observed abundant EZH2 expression and associated H3K27me3 modifications preferentially in the early committed virus-specific TFH cells compared to those in TH1 cells. Ablation of EZH2 in LCMV-specific CD4+ T cells leads to a selective impairment of early TFH cell fate commitment, but not late TFH differentiation or memory TFH maintenance. Mechanistically, EZH2 specifically stabilizes the chromatin accessibility of a cluster of genes that are important for TFH fate commitment, particularly B cell lymphoma 6 (Bcl6), and thus directs TFH cell commitment. Therefore, we identified the chromatin-modifying enzyme EZH2 as a novel regulator of early TFH differentiation during acute viral infection.
Keyphrases
- induced apoptosis
- cell cycle arrest
- long non coding rna
- transcription factor
- long noncoding rna
- liver failure
- cell fate
- mouse model
- regulatory t cells
- dna methylation
- poor prognosis
- oxidative stress
- cell death
- dna damage
- stem cells
- signaling pathway
- drug induced
- pi k akt
- cell proliferation
- cell therapy
- peripheral blood