使用激活色素状态持续存储运行的进入导致iTregs的不稳定性
Huiyun Lyu1,2, Guohua Yuan3,4, Xinyi Liu1,5
1Institute for Immunology, Beijing Key Lab for Immunological Research on Chronic Diseases, Tsinghua University, Beijing, China.
eLife
|December 6, 2023
概括
调控性T细胞 (Tregs) 的稳定性不同. 在体外诱导的Tregs (iTregs) 由于信号传递和染色质可访问性,比起来自胸腺的Tregs (tTregs) 不太稳定,影响Treg细胞治疗.
科学领域:
- 免疫学 免疫学 免疫学
- 细胞生物学 细胞生物学
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
背景情况:
- 调节性T细胞 (Tregs) 对于免疫抑制至关重要.
- 甲状腺起源的Tregs (tTregs) 和体外诱导的Tregs (iTregs) 具有不同的稳定性.
- 与tTregs不同的是,在炎症条件下,iTregs会失去其抑制表型.
研究的目的:
- 调查iTregs.表型不稳定的背后机制.
- 探索细胞信号和染色质可访问性在Treg稳定性中的作用.
- 确定改善Treg细胞治疗的潜在目标.
主要方法:
- 在tTregs,iTregs和常规T细胞 (Tconvs) 中对TCR触发,储存进入 (SOCE) 和NFAT转位进行比较分析.
- 评估不同Treg子集激活时的染色质可访问性变化.
- 研究NFAT与T助手 (TH) 基因的结合以及SOCE抑制对iTreg表型的影响.
主要成果:
- 在TCR触发时,tTregs表现出模糊的SOCE和NFAT信号,与iTregs和Tconvs不同.
- 激活时iTregs显示动态色素可访问性变化,具有可访问的T细胞激活和炎症基因.
- 在iTregs中NFAT激活驱动TH基因表达,导致不稳定,这可以通过抑制SOCE来部分挽救.
结论:
- 细胞信号传递 (SOCE-NFAT) 和染色质可访问性是Treg稳定性的关键决定因素.
- iTreg的不稳定性与它们激活T辅助基因的能力有关,模仿Tconv激活.
- 了解这些机制为提高Treg在治疗应用中的稳定性提供了新的途径.
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