监管性T细胞抑制剂程序采用转录因子IRF4来控制T (H) 2反应
Ye Zheng1, Ashutosh Chaudhry, Arnold Kas
1Howard Hughes Medical Institute, University of Washington, Seattle, Washington 98195, USA.
Nature
|February 3, 2009
概括
调节性T细胞 (Treg) 使用转录因子IRF4抑制T(H) 2免疫反应. 在Treg细胞中IRF4的损失选择性地损害了T(H) 2抑制,导致自身免疫病理.
科学领域:
- 免疫学 免疫学 免疫学
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
背景情况:
- 在感染或自身免疫过程中,T辅助 (T(H)) 细胞分化为效应子集 (T(H) 1,T(H) 2,T(H17).
- 调节性T细胞 (T(reg)) 抑制免疫反应,其分化由转录因子Foxp3.3指导.
- 福克斯p3 缺乏导致严重的自身免疫性疾病与增加的T (H) 1和T (H) 2细胞因子.
研究的目的:
- 研究转录因子IRF4在T细胞功能中的作用.
- 确定IRF4是否是Foxp3的直接目标,并调解T(reg) 抑制T(H) 2反应.
主要方法:
- 分析小鼠T细胞中的IRF4表达.
- 在T细胞中的Irf4基因的有条件切除.
- 评估T(H) 2细胞的反应,免疫球蛋白的产生和组织病理.
主要成果:
- 在老鼠T细胞中,高水平的IRF4需要Foxp3表达.
- 在T(reg) 细胞中切除Irf4导致T(H) 2反应失调,并产生依赖IL4的免疫球蛋白.
- 细胞特异性IRF4缺乏导致了特异性的自身免疫病理,其特征是血细胞透.
结论:
- ) 细胞利用IRF4专门抑制H) 2介导的免疫反应.
- 这种机制突显了T(reg) 细胞如何选择效应细胞分化机制来控制特定的免疫反应.
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