CCR4和CCR7不同调节小胞体局部化,对中央耐受性的结果不同
Yu Li1, Pablo Guaman Tipan1, Hilary J Selden1
1Department of Molecular Biosciences, The University of Texas at Austin, Austin, United States.
eLife
|June 2, 2023
概括
中央耐受性通过消除自身反应性T细胞来防止自身免疫. 这项研究揭示了CCR4和CCR7在引导T细胞到大脑中发挥不同的作用,以在不同发育阶段诱导耐受性.
科学领域:
- 免疫学 免疫学 免疫学
- T细胞生物学T细胞生物学
- 这是一种自身免疫力.
背景情况:
- 中央耐受性对于通过消除胸腺中自我反应性T细胞来预防自身免疫性至关重要.
- 胸细胞迁移到脑髓,以遇到由抗原呈现细胞 (APC) 呈现的自我抗原,以进行负面选择.
- 化基因受体CCR4和CCR7在这个过程中的作用尚未完全理解,它们可能具有不同的或冗余的功能.
研究的目的:
- 调查CCR4和CCR7在胸细胞髓入口和中央耐受性中的特定作用.
- 为了确定CCR4和CCR7在T细胞的负选择中是否有明显或冗余的作用.
- 阐明CCR4和CCR7在中央容忍度中的时间和功能差异.
主要方法:
- 在小鼠中同步的阳性选择试验.
- 胸细胞的双光子时隔显微镜.
- 量化T细胞受体 (TCR) 信号的亡性胸细胞.
主要成果:
- CCR4 和 CCR7 不同地调节不同后阳性选择胸细胞子集的髓积累和中心耐受性.
- 在阳性选择后的几个小时内,CCR4促进早期的髓入口和未成熟的胸细胞的删除.
- 在阳性选择几天后,CCR7促进晚期髓局部化和成熟胆小细胞的负选择.
结论:
- 在中央耐受性中,CCR4和CCR7在不同的发育阶段发挥着不同的,非冗余的作用.
- CCR4调解了激活APCs所呈现的自我抗原的耐受性,而CCR7则需要成熟的胸细胞选择.
- CCR7的表达不仅仅是髓局部化的迹象,并且提出了一种涉及明显APC相互作用的中央耐受性的修订模型.
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