滤泡辅助性T（Tfh）细胞是生发中心（GC）形成所需的CD4阳性效应T细胞亚群。

以前的研究表明，转录因子Bcl6在Tfh细胞中选择性表达，对Tfh细胞的分化至关重要。目前，Bcl6在Tfh发育中的分子机制仍了解较少。一些转录因子，例如STAT3、Ascl2、IRF4等被发现在调控Tfh细胞发育中有一定功能。但位于Bcl6调控上游，并且专属于Tfh细胞的通路仍然是领域内个一大空白。

2019年11月12日，清华大学医学院免疫学研究所董晨研究组在《免疫》在线发表了一项最新研究成果。他们发现转录因子Tox2通过调节染色质可及性来驱动滤泡辅助性T细胞（Tfh）的发育。

研究人员检查了在Tfh细胞定居过程中诱导Bcl6基因表达及其依赖性功能的分子途径。Tfh细胞中全基因组Bcl6占用的整合和差异基因表达分析表明，转录因子Tox2在Tfh细胞分化中具有重要作用。Tox2的异位表达足以驱动Bcl6表达和Tfh发育。在全基因组ChIP-seq分析中，与Tfh细胞分化和功能相关的Tox2结合位点，包括Bcl6。如通过ATAC-seq所测量的，Tox2结合与在这些位点上的染色质可及性增加有关。Tox2-/-小鼠表现出缺陷的Tfh分化，并且对Tox2和相关转录因子Tox的抑制均阻碍了Tfh分化。因此，Tox2-Bcl6信号轴建立了促进Tfh程序的正反馈调控通路。

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董晨，清华大学医学院院长。主要研究领域：T细胞分化和功能调控、细胞因子在炎症的功能及其机制、免疫耐受与肿瘤免疫治疗。（据清华大学医学院）

附：英文原文

Title: The Transcription Factor Tox2 Drives T Follicular Helper Cell Development via Regulating Chromatin Accessibility

Author: Wei Xu, Xiaohong Zhao, Xiaoshuang Wang, Han Feng, Mengting Gou, Wei Jin, Xiaohu Wang, Xindong Liu, Chen Dong

Issue&Volume: November 12, 2019

Abstract: T follicular helper (Tfh) cells provide essential help to B cells in germinal center(GC) reactions. Bcl6 is the obligatory lineage transcription factor in Tfh cells.Here, we examined the molecular pathways that induce Bcl6 gene expression and underscore Bcl6-dependent function during Tfh cell commitment.Integration of genome-wide Bcl6 occupancy in Tfh cells and differential gene expressionanalyses suggested an important role for the transcription factor Tox2 in Tfh celldifferentiation. Ectopic expression of Tox2 was sufficient to drive Bcl6 expressionand Tfh development. In genome-wide ChIP-seq analyses, Tox2-bound loci associatedwith Tfh cell differentiation and function, including Bcl6. Tox2 binding was associated with increased chromatin accessibility at these sites,as measured by ATAC-seq. Tox2/ mice exhibited defective Tfh differentiation, and inhibition of both Tox2 and therelated transcription factor Tox abolished Tfh differentiation. Thus, a Tox2-Bcl6axis establishes a transcriptional feed-forward loop that promotes the Tfh program.

DOI: 10.1016/j.immuni.2019.10.006

Source: https://www.cell.com/immunity/fulltext/S1074-7613(19)30450-9