Scholarlink

<p>In response to infections, naive CD8 T cells give rise to effector and memory T cells. However, eliciting long-lived memory CD8 T cells remains a challenge for many infections. DNA demethylation of cytosines within CpG dinucleotides by Tet enzymes is a key epigenetic mechanism that regulates short- and long-term transcriptional programs in cells. Currently, their roles in modulating CD8 T-cell effector and memory differentiation are unclear. Here, we report that developing CD8 T cells lacking Tet1/3 preferentially differentiate into short-lived effector and effector memory cells following acute infection. Using genome-wide analyses, mice in which Tet1/3 were ablated during T-cell development and mature CD8 T cells, respectively, we show that Tet1/3 regulates these cell fates by licensing the chromatin landscape of genes downstream of T-cell receptor activation during thymic T-cell maturation. However, in mature CD8 T cells, Tet1/3 are dispensable for effector and memory cell fates. These findings unveil context-specific roles of DNA demethylation, which are essential for defining pathways that contribute to CD8 memory T-cell generation in response to infections.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Developmental epigenetic programming by Tet1/3 determines peripheral CD8 T cell fate

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年4月2日

查看全文
  • Kara M Misel-Wuchter,
  • Andrew L Thurman,
  • Jordan T Johnson,
  • Athmane Teghanemt,
  • Neelam Gautam,
  • Alejandro A Pezzulo,
  • Jennifer R Bermick,
  • Noah S Butler,
  • Priya D Issuree

摘要

In response to infections, naive CD8 T cells give rise to effector and memory T cells. However, eliciting long-lived memory CD8 T cells remains a challenge for many infections. DNA demethylation of cytosines within CpG dinucleotides by Tet enzymes is a key epigenetic mechanism that regulates short- and long-term transcriptional programs in cells. Currently, their roles in modulating CD8 T-cell effector and memory differentiation are unclear. Here, we report that developing CD8 T cells lacking Tet1/3 preferentially differentiate into short-lived effector and effector memory cells following acute infection. Using genome-wide analyses, mice in which Tet1/3 were ablated during T-cell development and mature CD8 T cells, respectively, we show that Tet1/3 regulates these cell fates by licensing the chromatin landscape of genes downstream of T-cell receptor activation during thymic T-cell maturation. However, in mature CD8 T cells, Tet1/3 are dispensable for effector and memory cell fates. These findings unveil context-specific roles of DNA demethylation, which are essential for defining pathways that contribute to CD8 memory T-cell generation in response to infections.