胸膜上皮细胞采用谱系定义的转录因子来消除自反应性T细胞
Daniel A Michelson1, Koji Hase2, Tsuneyasu Kaisho3
1Department of Immunology, Harvard Medical School, Boston, MA 02115, USA.
Cell
|June 17, 2022
概括
骨髓胸膜上皮细胞 (mTEC) 使用谱系定义的转录因子来创建专门的"模拟"细胞. 这些细胞表达外周组织抗原 (PTA),对于建立自我耐受性和预防自身免疫性至关重要.
科学领域:
- 免疫学
- 细胞生物学
- 转录因子生物学
背景情况:
- 骨髓胸膜上皮细胞 (mTEC) 对于免疫耐受性至关重要.
- mTEC 异位表达成千上万的外周组织抗原 (PTA).
- 通过mTEC表达PTA的失败导致多器官自身免疫.
研究的目的:
- 研究mTEC表达PTA的机制.
- 确定不同的mTEC亚型及其在自我耐受性中的作用.
- 了解在mTEC分化和功能中的谱系定义转录因子的功能.
主要方法:
- 在单个mTEC中进行染色体可访问性测试.
- 对mTEC亚型的转录和组织学分析.
- 检测转录因子和Aire在模仿细胞功能中的作用.
主要成果:
- 确定了不同的mTEC亚型,称为模仿细胞,表达谱系定义转录因子 (例如,Grhl,FoxA,FoxJ1,Hnf4,Sox8,SpiB).
- 模拟细胞以反映额外胸膜细胞类型的方式表达PTA,同时保持mTEC的身份.
- 确定血统的TF对于模仿细胞积累和PTA表达至关重要;Aire起着部分作用.
- 在模拟细胞中表达模型抗原有效诱导T细胞耐受性.
结论:
- mTECs利用谱系定义TF来产生模仿细胞.
- 模仿细胞对于表达PTA和诱导自我耐受性至关重要.
- 这种机制通过在胸膜分化过程中培养T细胞来防止自身免疫.
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