酸代谢作为饮食MR1配体的来源
David O'Sullivan1,2, Carl J H Wang3, Jeffry S Tang1,2
1Malaghan Institute of Medical Research, Wellington, New Zealand.
Journal of immunology (Baltimore, Md. : 1950)
|February 27, 2026
概括
饮食中的类代谢物,如酸,被确定为MR1的配体. 这些配体可以调节粘膜相关的不变T细胞 (MAIT) 激活,影响免疫反应.
科学领域:
- 免疫学 免疫学 免疫学
- 代谢学 代谢学 代谢学
- 结构生物学 结构生物学
背景情况:
- 主性组织相容性复合体 (MHC) 类I类类似分子MR1向MR1受限的T细胞呈现代谢物,包括粘膜相关的不变T细胞 (MAIT).
- MAIT细胞在免疫力和恒常性中起着至关重要的作用,识别细菌的 рибофлавин衍生的抗原.
- 目前尚不清楚MR1受限配体的全谱.
研究的目的:
- 调查饮食中的类代谢物作为MR1的潜在配体.
- 识别新型MR1配体并了解它们与MR1和MAIT细胞的相互作用.
主要方法:
- 选一种饮食中的类代谢物库,以检测MR1连接体活性.
- 使用具有竞争力的MAIT细胞抑制测定与细胞系和人类初级血液细胞.
- 采用光偏振结合试验来确认MR1-联体相互作用.
- 通过MR1.1确定基酸呈现的结构基础.
主要成果:
- 埃拉基坦宁的肠道微生物代谢物,包括埃拉基酸 (EA),乌罗丁D (UroD) 和UroM5,被确定为潜在的MR1配体.
- EA,UroM5,urolithin C (UroC) 和urolithin B (UroB) 已经证明它们与MR1.1结合.
- 建立了MR1对EA呈现的结构基础.
- 饮食EA代谢产生MR1配体,抑制T细胞受体依赖MAIT细胞激活.
结论:
- 饮食中的类化合物,特别是基酸等基坦宁的代谢产物,作为MR1连接体.
- 这些饮食中的MR1配体可以调节MAIT细胞激活,这表明饮食,肠道微生物群和免疫细胞功能之间存在联系.
- 这些发现扩大了已知的MR1配体库,并突出了它们的饮食起源.
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