空气驱动由骨髓胸膜上皮细胞驱动类固醇激素生物合成
Matthew D Taves1, Kaitlynn M Donahue1, Jing Bian2
1Laboratory of Immune Cell Biology, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA.
Science immunology
|August 18, 2023
概括
胸腺通过神经髓TEC中的依赖空气的途径产生葡萄糖皮质,影响T细胞选择. 这种Aire功能平衡负选择,可能扩大T细胞谱.
科学领域:
- 免疫学 免疫学 免疫学
- 内分泌学 在内分泌学.
- 分子生物学分子生物学
背景情况:
- 胸膜上皮细胞 (TECs) 对于T细胞发育至关重要.
- 由TECs产生的葡萄糖皮质体调节了胸细胞选择.
- 转录因子Aire通过诱导组织受限抗原 (TRAs) 对于中央耐受性至关重要.
研究的目的:
- 为了确定胸腺内葡萄糖皮质激素的来源.
- 为了研究Aire在甲状腺中产生生物活性类固醇中的作用.
主要方法:
- 创建了一个模拟记者鼠标模型,用光标签标记Cyp11b1.1.
- 使用mScarlet标记来追踪TEC中的Cyp11b1表达.
- 进行了转录基因分析和培养的胸膜扩展剂.
主要成果:
- 糖皮质醇合成的关键基因Cyp11b1在髓状TEC (mTEC) 中特别表达,特别是Aire阳性mTEC.
- 空气缺乏显著减少了类固醇酶转录和类固醇生产的表达.
- 葡萄皮质类固醇和性类固醇是由培养的提米以依赖于空气的方式分泌出来的.
结论:
- 艾尔诱导mTECs中的葡萄皮质激素的产生,对抗负选择并扩大T细胞受体 (TCR) 谱.
- 艾瑞具有双重作用:诱导TRAs进行负选择,并诱导抗拒它的葡萄皮质激素.
- 空气可能会调节其他生物活性分子,这表明它在甲状腺发育和功能中起着更广泛的作用.
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