澳大利亚墨尔本大学Laura K. Mackay等研究人员合作发现，不同的表观基因组景观是组织特异性记忆T细胞分化的基础。该研究于2024年7月22日在线发表于国际一流学术期刊《免疫》。

研究人员通过四种不同感染模型的七个非淋巴器官中分离出CD8⁺ T细胞，研究了其表观遗传景观，并与其循环的T细胞对应物进行了对比。通过单细胞转座酶可及性染色质测序（scATAC-seq），研究人员发现组织驻留记忆性T细胞（T_RM细胞）和循环记忆性T细胞（T_CIRC细胞）沿着不同的表观遗传轨迹发展。研究人员确定了T_RM细胞发育的器官特异性转录调控因子，包括FOSB、FOS、FOSL1和BACH2，并定义了T_RM细胞在各器官中的共同表观遗传特征。

最后，研究人员发现尽管终末耗竭性T细胞（T_EX细胞）与T_RM细胞共享可及性的调控元件，但T_EX细胞由特定于T_EX的表观遗传特征定义，这些特征在T_RM细胞中缺失。总体而言，这一全面的数据资源显示，T_RM细胞发育伴随着动态的转录组变化和染色质可及性变化，这些变化指导了组织适应性和功能独特的T细胞状态。

据悉，记忆性CD8⁺ T细胞池包含在表型和转录方面具有异质性的亚群，这些亚群具有专门的功能和循环模式。

附：英文原文

Title: Distinct epigenomic landscapes underlie tissue-specific memory T cell differentiation

Author: Frank A. Buquicchio, Raissa Fonseca, Patrick K. Yan, Fangyi Wang, Maximilien Evrard, Andreas Obers, Jacob C. Gutierrez, Colin J. Raposo, Julia A. Belk, Bence Daniel, Pirooz Zareie, Kathryn E. Yost, Yanyan Qi, Yajie Yin, Katherine F. Nico, Flora M. Tierney, Michael R. Howitt, Caleb A. Lareau, Ansuman T. Satpathy, Laura K. Mackay

Issue&Volume: 2024-07-22

Abstract: The memory CD8+ T cell pool contains phenotypically and transcriptionally heterogeneous subsets withspecialized functions and recirculation patterns. Here, we examined the epigeneticlandscape of CD8+ T cells isolated from seven non-lymphoid organs across four distinct infection models,alongside their circulating T cell counterparts. Using single-cell transposase-accessiblechromatin sequencing (scATAC-seq), we found that tissue-resident memory T (TRM) cells and circulating memory T (TCIRC) cells develop along distinct epigenetic trajectories. We identified organ-specifictranscriptional regulators of TRM cell development, including FOSB, FOS, FOSL1, and BACH2, and defined an epigeneticsignature common to TRM cells across organs. Finally, we found that although terminal TEX cells share accessible regulatory elements with TRM cells, they are defined by TEX-specific epigenetic features absent from TRM cells. Together, this comprehensive data resource shows that TRM cell development is accompanied by dynamic transcriptome alterations and chromatinaccessibility changes that direct tissue-adapted and functionally distinct T cellstates.

DOI: 10.1016/j.immuni.2024.06.014

Source: https://www.cell.com/immunity/abstract/S1074-7613(24)00320-0