表达转录因子T-bet的调节性T细胞的稳定性和功能
Andrew G Levine1, Alejandra Mendoza1, Saskia Hemmers1
1Howard Hughes Medical Institute, Immunology Program, and Ludwig Center, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA.
Nature
|June 14, 2017
概括
表达T-贝特转录因子的调节性T细胞是稳定的,对抑制T辅助1自身免疫是至关重要的. 这些T-bet+调节T细胞对于维持免疫耐受性至关重要.
科学领域:
- 免疫学
- 细胞生物学
背景情况:
- 适应性免疫涉及CD4 T细胞分化成效应子集 (T助手1,T助手2,T助手17),由T-bet等转录因子定义.
- 由Foxp3指定的调节性T (Treg) 细胞具有抗炎作用,但可以表达效应性T细胞转录因子,表明功能性可塑性.
研究的目的:
- 研究小鼠调控T细胞中的T-bet表达的稳定性和功能.
- 要确定Treg细胞中的T-bet表达是否表明稳定的分化或可逆的可塑性.
主要方法:
- 在稳定状态和感染期间诱导小鼠Treg细胞的T-bet表达.
- 在非允许条件下评估T-bet表达的稳定性.
- 评估T-bet+ Treg细胞损失或T-bet表达操纵对免疫反应和自身免疫的功能后果.
主要成果:
- 在Treg细胞中T-bet表达,一旦诱导,即使在非允许条件下也变得高度稳定.
- 失去或消除表达T-bet的Treg细胞,但不仅仅是T-bet表达,导致严重的T助手1自身免疫.
- 其余的T- bet+ Treg细胞特别抑制了T辅助1和CD8T细胞的激活,与它们与效应T细胞的局部相关.
结论:
- T-bet+ Treg细胞具有关键的免疫抑制功能.
- 在Treg细胞群体内的功能异质性对于免疫耐受性至关重要.
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