生物
效应器
BCL6公司
人口
CD8型
染色质
基因表达
细胞分化
基因
细胞生物学
遗传学
免疫学
免疫系统
B细胞
生发中心
人口学
社会学
抗体
作者
Quynh Nguyen,Kennidy K. Takehara,Tianda Deng,Shannon O’Shea,Maximilian Heeg,Kyla Omilusik,J. Justin Milner,Sara Quon,Matthew E. Pipkin,Jinyong Choi,Shane Crotty,Ananda W. Goldrath
出处
期刊:Science immunology
[American Association for the Advancement of Science (AAAS)]
日期:2023-05-26
卷期号:8 (83)
被引量:1
标识
DOI:10.1126/sciimmunol.abq7486
摘要
After resolution of infection, T cells differentiate into long-lived memory cells that recirculate through secondary lymphoid organs or establish residence in tissues. In contrast to CD8+ tissue-resident memory T cells (TRM), the developmental origins and transcriptional regulation of CD4+ TRM remain largely undefined. Here, we investigated the phenotypic, functional, and transcriptional profiles of CD4+ TRM in the small intestine (SI) responding to acute viral infection, revealing a shared gene expression program and chromatin accessibility profile with circulating TH1 and the progressive acquisition of a mature TRM program. Single-cell RNA sequencing identified heterogeneity among established CD4+ TRM, which were predominantly located in the lamina propria, and revealed a population of cells that coexpressed both effector- and memory-associated genes, including the transcriptional regulators Blimp1, Id2, and Bcl6. TH1-associated Blimp1 and Id2 and TFH-associated Bcl6 were required for early TRM formation and development of a mature TRM population in the SI. These results demonstrate a developmental relationship between TH1 effector cells and the establishment of early TRM, as well as highlighted differences in CD4+ versus CD8+ TRM populations, providing insights into the mechanisms underlying the origins, differentiation, and persistence of CD4+ TRM in response to viral infection.
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