在类风湿性关节炎中代谢检查点
Cornelia M Weyand1, Jörg J Goronzy2
1Department of Medicine, Mayo Clinic Alix School of Medicine, Rochester, MN, 55905, USA; Department of Immunology, Mayo Clinic College of Medicine and Science, Rochester, MN, 55905, USA; Department of Cardiovascular Medicine, Mayo Clinic Alix School of Medicine, Rochester, MN, USA; Department of Medicine, Stanford University School of Medicine, Stanford, CA, 94305, USA.
Seminars in arthritis and rheumatism
|November 16, 2024
概括
风湿性关节炎的免疫细胞通过利用谷氨来适应关节的低葡萄糖环境. 在T细胞和巨细胞中的代谢重编程驱动了类风湿性关节炎的炎症和组织损伤.
科学领域:
- 免疫学 免疫学 免疫学
- 代谢途径 代谢途径
- 自身免疫性疾病是一种自身免疫性疾病.
背景情况:
- 类风湿性关节炎 (RA) 是一种全身性自身免疫性疾病,影响0.5-1%的人口.
- 尽管取得了进展,但RA仍然无法治愈,导致严重的发病率.
- HLAII类多态突出T细胞作为关键驱动器,而像巨细胞 (MΦ) 这样的先天性免疫细胞有助于炎症.
研究的目的:
- 为了总结RA关节内的代谢条件.
- 阐明影响RAT细胞和MΦ效应器功能的代谢回路.
主要方法:
- 综述当前关于类风湿性关节炎细胞代谢的知识.
- 在RA关节环境中的T细胞和巨细胞代谢适应的分析.
主要成果:
- RA 关节缺乏葡萄糖,有利于细胞利用像谷氨酸这样的非葡萄糖燃料.
- 雷性T细胞表现出低的线粒体功能,受损的ATP生产,并由于mtDNA修复缺陷增加了自身活性.
- 雷性病巨体显示高功能线粒体,高调节的HLA-DR,并通过RFX5和GLUD1通过增强的谷氨酸溶解进行抗原呈现和生存.
结论:
- 代谢重编程对于RA关节的免疫细胞存活和功能至关重要.
- 这些适应促进免疫刺激,组织入侵,并维持类风湿性突炎.
- 准细胞代谢是一种潜在的RA治疗策略.
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