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淋巴细胞从胸腺和外围淋巴体器官的退出取决于S1P受体1
Mehrdad Matloubian1, Charles G Lo, Guy Cinamon
1Howard Hughes Medical Institute and Department of Microbiology, University of California San Francisco, 513 Parnassus Avenue, San Francisco, California 94143-0414, USA.
Nature
|January 23, 2004
概括
氨酸-1-酸盐受体1 (S1P1) 对于T细胞和B细胞的运动至关重要. 这项研究揭示了S1P1控制了淋巴细胞从胆小板和淋巴体器官的退出,这对于免疫细胞贩运至关重要.
科学领域:
- 免疫学 免疫学 免疫学
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
背景情况:
- 适应性免疫依赖于淋巴细胞在淋巴体器官和组织之间循环.
- 控制淋巴细胞从淋巴体器官退出的机制尚未完全理解.
- 作为一种免疫抑制剂的FTY720,通过与基-1-酸盐 (S1P) 受体相互作用,影响淋巴细胞贩运.
研究的目的:
- 研究S1P受体,特别是S1P受体1 (S1P1) 在正常免疫细胞贩运中的作用.
- 阐明调节淋巴细胞从胸腺和二级淋巴体器官出血的机制.
- 解释免疫抑制药物FTY720.20的作用机制.
主要方法:
- 在造血细胞中缺乏S1P1的生成小鼠.
- 进行了收养细胞移植实验.
- 分析了胸腺,血液,淋巴和淋巴体器官中的淋巴细胞群.
- 在淋巴细胞发育和激活过程中研究了S1P1表达和化学反应反应.
主要成果:
- 缺少S1P1的小鼠显示出完全没有外围T细胞,这是由于胸膜出口受损.
- 血液和淋巴细胞中B细胞缺乏,这表明S1P1在它们的退出中发挥了作用.
- 从本质上来说,S1P1是T和B细胞从淋巴体器官的退出所必需的.
- 在胸膜退出之前,S1P1表达是上调的,在外周激活时是下调的,与细胞保留相关.
- FTY720治疗模仿了这些发现,通过降低S1P1的调节,导致淋巴细胞封存.
结论:
- S1P1对于淋巴细胞再循环至关重要.
- S1P1调节了淋巴细胞从胸腺和外围淋巴体器官的退出.
- 了解S1P1功能澄清了FTY720免疫抑制的机制,并为免疫细胞贩运控制策略提供了信息.
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