PD-1从鱼保存到人类:对PD-1,PD-L1,PD-L2和SHP-2进化的新见解
Ryohei Kondo1, Kohei Kondo2, Kei Nabeshima3
1Biosafety Division, Research Institute, National Center for Geriatrics and Gerontology, Obu, Aichi, Japan.
Frontiers in immunology
|June 12, 2025
概括
免疫检查点分子编程细胞死亡蛋白1 (PD-1) 和它的连接物有古老的起源,在鱼类中发现了保存的功能. 这项研究揭示了PD-1进化及其在脊椎动物之间的相互作用的新见解.
科学领域:
- 进化免疫学的进化免疫学
- 分子进化是分子进化的过程.
- 进行比较的基因组学.
背景情况:
- 编程细胞死亡蛋白1 (PD-1) 是一个关键的免疫检查点分子.
- 以前认为PD-1只存在于四足动物中.
- 了解PD-1进化为免疫系统发育提供了洞察力.
研究的目的:
- 在非四足动物脊椎动物中识别和分析PD-1基因及其配体.
- 研究PD-1信号传导的进化历史和保存功能.
- 探索免疫检查点路径中特定于血统的适应.
主要方法:
- 基因组数据库的生物信息分析.
- 对PD-1及其相互作用伙伴 (PD-L1,PD-L2,SHP-2) 的分子分析.
- 遗传学分析和序列模式识别.
主要成果:
- 在骨和软骨鱼类中发现了PD-1基因,这表明其起源很古老.
- 保存的序列动图表明PD-1与PD-L1和SHP-2的古代结合模式.
- 鱼类中的PD-1转录与T细胞标记物共同表达,表明免疫检查点功能得到保护.
- 发现一种类似PD-1的基因 (SHP-2L) 从鱼保存到哺乳动物.
结论:
- PD-1及其核心结合机制是古老的,早于四足动物.
- PD-1的免疫检查点功能似乎在的脊椎动物中得到保护.
- 对比分析揭示了PD-1进化过程中既保留的特征,又出现了新的适应.
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