美国芝加哥大学Andrew S. Koh小组发现，PU.1和BCL11B先后与RUNX1合作来锚定mSWI/SNF以调整T细胞效应器的格局。2024年4月17日，《自然—免疫学》杂志在线发表了这项成果。

研究人员揭示了染色质引物在指定效应T细胞功能输出中的作用，发现在效应T细胞中活跃的顺式调控格局大多在T细胞抗原受体表达之前的发育早期就已定型。研究人员确定了支撑这种静止状态的两种主要机制：转录因子RUNX1和PU.1招募核小体重塑因子哺乳动物SWItch/Sucrose Non-Fermentable（mSWI/SNF）转录因子BCL11B通过“中继”作用在PU.1沉默后，与RUNX1一起维持染色质重塑复合物mSWI/SNF的占据。

这些机制确定了T细胞在其个体发育早期获得激发特化效应器功能潜力的模式，并强调了将外在线索整合到发育特定内在程序中的重要性。

据介绍，适应性免疫依赖于淋巴细胞激发的特化效应功能，但抗原识别如何通过非特异性信号中间体激活适当的效应反应尚不清楚。

附：英文原文

Title: PU.1 and BCL11B sequentially cooperate with RUNX1 to anchor mSWI/SNF to poise the T cell effector landscape

Author: Gamble, Noah, Bradu, Alexandra, Caldwell, Jason A., McKeever, Joshua, Bolonduro, Olubusayo, Ermis, Ebru, Kaiser, Caroline, Kim, YeEun, Parks, Benjamin, Klemm, Sandy, Greenleaf, William J., Crabtree, Gerald R., Koh, Andrew S.

Issue&Volume: 2024-04-17

Abstract: Adaptive immunity relies on specialized effector functions elicited by lymphocytes, yet how antigen recognition activates appropriate effector responses through nonspecific signaling intermediates is unclear. Here we examined the role of chromatin priming in specifying the functional outputs of effector T cells and found that most of the cis-regulatory landscape active in effector T cells was poised early in development before the expression of the T cell antigen receptor. We identified two principal mechanisms underpinning this poised landscape: the recruitment of the nucleosome remodeler mammalian SWItch/Sucrose Non-Fermentable (mSWI/SNF) by the transcription factors RUNX1 and PU.1 to establish chromatin accessibility at T effector loci; and a ‘relay’ whereby the transcription factor BCL11B succeeded PU.1 to maintain occupancy of the chromatin remodeling complex mSWI/SNF together with RUNX1, after PU.1 silencing during lineage commitment. These mechanisms define modes by which T cells acquire the potential to elicit specialized effector functions early in their ontogeny and underscore the importance of integrating extrinsic cues to the developmentally specified intrinsic program.

DOI: 10.1038/s41590-024-01807-y

Source: https://www.nature.com/articles/s41590-024-01807-y