美国哈肯萨克大学医学中心薛海晖和中国医学科学院-北京协和医学院单强团队合作，揭示转录辅因子Tle3互相调控效应和中央记忆CD8+ T细胞命运。这一研究成果发表在2024年1月18日出版的国际学术期刊《自然—免疫学》上。

本研究表明，转录辅助因子Tle3通过抗原应答CD8+ T细胞基因组的动态重分布，对TEM和TCM细胞命运和谱系稳定性进行了关键调控。基因消融Tle3促进CD8+ TCM细胞的形成，而牺牲CD8+ TEM细胞。谱系追踪显示，Tle3缺陷CD8+ TEM细胞加速转化为CD8+ TCM细胞，同时保持强大的回忆能力。

Tle3作为Tbet的共激活因子，增加CD8+ TEM细胞特征位点的染色质开放，激活CD8+ TEM细胞特征基因转录，同时与Runx3和Tcf1结合，限制CD8+ TCM细胞特征分子特征。因此，Tle3整合了多种转录因子的功能来保护CD8+ TEM细胞的谱系保真度，操纵Tle3活性可能有利于CD8+ TCM细胞的产生。

据了解，抗原经历的CD8+ T细胞形成效应T细胞和中枢记忆T细胞(分别为TEM细胞和TCM细胞);然而，控制它们谱系可塑性的机制仍然不完全清楚。

附：英文原文

Title: The transcriptional cofactor Tle3 reciprocally controls effector and central memory CD8+ T cell fates

Author: Zhao, Xin, Hu, Wei, Park, Sung Rye, Zhu, Shaoqi, Hu, Shengen Shawn, Zang, Chongzhi, Peng, Weiqun, Shan, Qiang, Xue, Hai-Hui

Issue&Volume: 2024-01-18

Abstract: Antigen-experienced CD8+ T cells form effector and central memory T cells (TEM and TCM cells, respectively); however, the mechanism(s) controlling their lineage plasticity remains incompletely understood. Here we show that the transcription cofactor Tle3 critically regulates TEM and TCM cell fates and lineage stability through dynamic redistribution in antigen-responding CD8+ T cell genome. Genetic ablation of Tle3 promoted CD8+ TCM cell formation at the expense of CD8+ TEM cells. Lineage tracing showed that Tle3-deficient CD8+ TEM cells underwent accelerated conversion into CD8+ TCM cells while retaining robust recall capacity. Tle3 acted as a coactivator for Tbet to increase chromatin opening at CD8+ TEM cell-characteristic sites and to activate CD8+ TEM cell signature gene transcription, while engaging Runx3 and Tcf1 to limit CD8+ TCM cell-characteristic molecular features. Thus, Tle3 integrated functions of multiple transcription factors to guard lineage fidelity of CD8+ TEM cells, and manipulation of Tle3 activity could favor CD8+ TCM cell production.

DOI: 10.1038/s41590-023-01720-w

Source: https://www.nature.com/articles/s41590-023-01720-w