Role of nsd2 in Follicular helper T cells

Follicular helper T cell (Tfh) provide essential help for humoral immune response. However, how Tfh differentiation is epigenetically regulated remains incompletely understood. Here we found that H3K36me2 methyltransferase Nsd2 is required for Tfh differentiation. Lack of Nsd2 leads to reduced Tfh generation and germinal center response. Mice with Nsd2 deficiency in T cells have reduced capability of chronic virus control. To understand the molecular mechanism by which Nsd2 regulates Tfh differentiation, RNA-seq analysis of Nsd2 wildtype and knockout Tfh cells were performed. CD4+CXCR5+PD1+ Tfh cells were sorted from wildtype (WT) and CD4Cre+Nsd2fl/fl (KO) mice for RNA-seq analysis to identify the differential expressed genes.

滤泡辅助性T细胞（Follicular helper T cell, Tfh）可为体液免疫应答提供关键辅助功能。然而，Tfh分化的表观遗传调控机制仍未完全阐明。本研究发现，H3K36me2甲基转移酶Nsd2是Tfh分化所必需的因子。Nsd2缺失会导致Tfh生成减少以及生发中心应答受损。T细胞中Nsd2缺陷的小鼠，其慢性病毒控制能力有所下降。为解析Nsd2调控Tfh分化的分子机制，我们对Nsd2野生型与敲除型Tfh细胞开展了RNA测序（RNA-seq）分析。本研究从野生型（WT）小鼠以及CD4Cre+Nsd2fl/fl（KO）小鼠中分选得到CD4+CXCR5+PD1+ Tfh细胞，通过RNA-seq分析以筛选差异表达基因（differentially expressed genes）。