通过H3K27乙化进行抗体类交换重组,MCT1控制的酸盐代谢对于抗体类交换重组至关重要
Wenna Chi1,2, Na Kang3,4, Linlin Sheng1
1School of Pharmaceutical Sciences, Key Laboratory of Bioorganic Phosphorus Chemistry and Chemical Biology (Ministry of Education), Tsinghua University, Beijing, 100084, China.
Nature communications
|January 3, 2024
概括
单碳酸盐载体1 (MCT1) 对于B细胞抗体产生至关重要. 其缺乏通过改变葡萄糖代谢和抑制AID转录来损害IgG反应,突出显示MCT1是SLE等自身免疫性疾病的治疗标.
科学领域:
- 免疫学 免疫学 免疫学
- 细胞的新陈代谢
- 分子生物学分子生物学
背景情况:
- 单碳酸盐转运体1 (MCT1) 对于细胞能量供应至关重要.
- 在激活的B细胞中,MCT1的表达很高,但其在与葡萄糖代谢相关的抗体产生中的作用尚不清楚.
研究的目的:
- 研究MCT1在B细胞代谢和抗体产生中的功能作用.
- 阐明MCT1影响类交换重组 (CSR) 和IgG反应的机制.
主要方法:
- 使用Mct1缺乏的小鼠 (Mct1f/fMb1Cre) 来研究B细胞特异性MCT1缺乏.
- 对激活的B细胞进行了代谢流量分析.
- 评估了类切换重组 (CSR),IgG抗体的产生,激活诱导的细胞氨酸脱氨酶 (AID) 表达和H3K27乙化.
- 在人类全身性红斑狼 (SLE) 患者和小鼠狼模型中检查了MCT1表达.
主要成果:
- 在免疫接种后,B细胞特异性MCT1缺乏会损害IgG抗体反应和CSR.
- 缺乏MCT1的B细胞表现出从糖解转向氧化酸化的代谢转变.
- 激活诱导的cytidine deaminase (AID) 表达在MCT1缺乏的B细胞中被抑制,这是由于减少了pyruvate水平.
- MCT1维持了H3K27乙化最佳的酸盐水平,这对于AID转录至关重要.
- 在SLE患者中,MCT1被上调,其缺乏在小鼠模型中改善了狼症状.
结论:
- 通过AID转录的表观遗传调节,MCT1介导的酸盐代谢对于IgG抗体CSR至关重要.
- MCT1在B细胞激活和抗体产生中起着至关重要的作用.
- MCT1代表了疫苗开发和SLE治疗的潜在治疗标.
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