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环境因素调节呼吸道驻留记忆T细胞的表观重编程
作者:小柯机器人 发布时间:2020/1/22 13:31:47

美国埃默里大学医学院Jacob E. Kohlmeier小组的一项最新研究表明,环境因素调节呼吸道驻留记忆CD8+T细胞的表观遗传重编程。该研究2020年1月17日在线发表于国际一流学术期刊《自然—免疫学》。

研究人员发现,呼吸道环境驱动转录和表观遗传变化,这些变化专门调节呼吸道的组织驻留记忆T细胞(TRM细胞)的溶细胞功能,并由于氨基酸饥饿和整合应激反应的激活而促进细胞凋亡。呼吸道TRM细胞与转移到呼吸道的脾效应记忆T细胞之间的比较表明,环境是激活这些途径所必需的,但不会诱导TRM细胞谱系重编程。重要的是,在营养丰富的环境中,呼吸道TRM细胞中整合应激反应的激活被逆转了。这些数据定义了不同肺TRM细胞群体的遗传程序,并表明局部环境因素改变了呼吸道TRM细胞,以限制溶细胞功能并促进细胞死亡,最终导致肺中TRM细胞减少。
 
据悉,TRM细胞对于呼吸道病原体的细胞免疫至关重要,并且驻留在呼吸道和间质中。
 
附:英文原文

Title: Environmental cues regulate epigenetic reprogramming of airway-resident memory CD8 + T cells

Author: Sarah L. Hayward, Christopher D. Scharer, Emily K. Cartwright, Shiki Takamura, Zheng-Rong Tiger Li, Jeremy M. Boss, Jacob E. Kohlmeier

Issue&Volume: 2020-01-17

Abstract: Tissue-resident memory T cells (TRM cells) are critical for cellular immunity to respiratory pathogens and reside in both the airways and the interstitium. In the present study, we found that the airway environment drove transcriptional and epigenetic changes that specifically regulated the cytolytic functions of airway TRM cells and promoted apoptosis due to amino acid starvation and activation of the integrated stress response. Comparison of airway TRM cells and splenic effector-memory T cells transferred into the airways indicated that the environment was necessary to activate these pathways, but did not induce TRM cell lineage reprogramming. Importantly, activation of the integrated stress response was reversed in airway TRM cells placed in a nutrient-rich environment. Our data defined the genetic programs of distinct lung TRM cell populations and show that local environmental cues altered airway TRM cells to limit cytolytic function and promote cell death, which ultimately leads to fewer TRM cells in the lung.

DOI: 10.1038/s41590-019-0584-x

Source: https://www.nature.com/articles/s41590-019-0584-x

期刊信息

Nature Immunology:《自然—免疫学》,创刊于2000年。隶属于施普林格·自然出版集团,最新IF:23.53
官方网址:https://www.nature.com/ni/
投稿链接:https://mts-ni.nature.com/cgi-bin/main.plex