人类致病性类似的Th17细胞的迁移停止和超内皮贩运是由不同位置的化学因子调解的
Farhat Parween1, Satya P Singh1, Nausheen Kathuria1
1Inflammation Biology Section, Laboratory of Molecular Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
Nature communications
|February 25, 2025
概括
表达CCR6和CCR2的人类T细胞与多发性硬化症有关,并可能导致炎症. T细胞迁移到组织中需要特定的化学激素梯度,与表面结合的化学激素调解逮捕和梯度驱动迁移.
科学领域:
- 免疫学 免疫学 免疫学
- 神经科学是一个神经科学.
- 细胞生物学 细胞生物学
背景情况:
- 人类Th17/类型17细胞表达CCR6,但CCR6和其他化学受体在它们的扩散中的作用尚未完全理解.
- 化基因受体在免疫细胞的运输和功能中起着至关重要的作用.
研究的目的:
- 为了研究化学因子受体CCR6和CCR2在人类Th17细胞扩散中的功能.
- 确定化基因梯度影响T细胞迁移和结的机制.
主要方法:
- 对人体外围血液中CD4+ T细胞的分析,包括共同表达CCR的CD4+CCR6+ T细胞2.
- 评估多发性硬化症患者脑脊液中的基因表达.
- 在体外通过内皮细胞迁移 (TEM) 的测定使用激活内皮细胞单层和流室.
- 工程仿真CCR2配体研究结合和迁移效应.
主要成果:
- CD4+CCR6+CCR2+T细胞表现出致病的Th17特征,在没有T细胞受体激活的情况下产生炎症性细胞因子,并在多发性硬化症脑脊液中表现出致病性相关的基因表达增加.
- 这些T细胞有效地经历了超内皮迁移 (TEM).
- 对于CCR5,CCR6和CXCR3的表面结合联体调解T细胞的停止,而CCR2联体则调解TEM.
- 工程设计的CCR2配体结合了内皮细胞的葡萄糖氨基酸,导致TEM停止,但阻断TEM.
结论:
- 为了阻止T细胞迁移,需要化学基因与内皮细胞表面结合.
- 超内皮细胞迁移 (TEM) 是由一个超内皮细胞化学基因梯度驱动的.
- 在多发性硬化症等疾病中,CCR6和CCR2在致病性T细胞贩运中发挥着不同的作用.
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