RORα负面调节BCG诱导的训练免疫
Gizem Kilic1, Vasiliki Matzaraki1, Ozlem Bulut1
1Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, The Netherlands.
Cellular immunology
|August 19, 2024
概括
这种RORA基因变异影响了在Bacillus Calmette-Guérin (BCG) 疫苗接种后的训练免疫反应. 抑制RORα可以增强训练免疫力,这表明它在免疫反应和疫苗接种有效性中的作用.
科学领域:
- 免疫学 免疫学 免疫学
- 遗传学 是一个遗传学.
- 分子生物学分子生物学
背景情况:
- 训练有素的免疫包括持久的先天性免疫细胞变化,增强对次要挑战的反应.
- 表观遗传,转录和代谢重编程是训练免疫发展的关键机制.
研究的目的:
- 为了研究基因变异对培训免疫力的影响,在Bacillus Calmette-Guérin (BCG) 疫苗接种后.
- 在人类外周血液单核细胞 (PBMC) 中识别与BCG诱导的训练免疫的遗传关联.
主要方法:
- 对基因变异的分析,特别是RORA基因中的多态性,与BCG诱导的训练免疫有关.
- 在人类PBMC中测量细胞因子的产生,细胞形态,活性氧物种 (ROS) 和乳酸生产.
- 药理上抑制RORα和阻断乳酸脱酶A (LDHA) 和糖解.
主要成果:
- 在RORA基因多态和BCG诱导的训练免疫之间发现了强烈的关联.
- 循环中的自然RORα激动剂与训练的免疫力负相关.
- 在PBMC中药理性RORα抑制增强了BCG诱导的训练免疫力,增加了细胞因子的产生和改变细胞特征.
- 阻断LDHA和糖解减少了BCG训练的细胞中细胞因子的产生,这些细胞接受了RORα激动剂的治疗.
结论:
- RORα在训练免疫力中起着重要作用.
- RORα活性会影响人类接种疫苗的反应和潜在的疾病结果.
- 进一步调查RORα在训练免疫力中的作用是有必要的.
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