神经刺激调节B细胞上不同的乙胆受体,并限制生殖中心的反应
Izumi Kurata-Sato1, Ibrahim T Mughrabi2, Minakshi Rana1
1Center for Autoimmune Musculoskeletal and Hematopoietic Diseases, The Feinstein Institutes for Medical Research, Northwell Health, Manhasset, NY, USA.
Science advances
|April 26, 2024
概括
神经刺激 (VNS) 通过影响B细胞和卵泡树突细胞,损害了抗体的产生. 乙烯基胆是一种
科学领域:
- 免疫学 免疫学 免疫学
- 神经科学是一个神经科学.
- 细胞生物学 细胞生物学
背景情况:
- 神经的激活刺激了脏中的乙胆的产生.
- 迷走神经刺激 (VNS) 对适应性免疫,特别是B细胞反应的影响,仍然在很大程度上未被描述.
- 了解免疫反应的神经控制对于开发新型治疗策略至关重要.
研究的目的:
- 在小鼠模型中研究慢性迷走神经刺激 (VNS) 对T依赖B细胞反应的影响.
- 阐明VNS影响B细胞功能,生殖中心形成和抗体产生的特定机制.
主要方法:
- 使用慢性迷走神经刺激 (VNS) 的小鼠模型.
- 评估了抗体标位,生殖中心 (GC) B细胞种群和血细胞分化.
- 在GC B细胞和卵泡树突细胞 (FDC) 中分析了基因和蛋白质表达.
- 进行了体外研究,以检查尼古丁乙胆受体 (nAChRs) 在B细胞上的作用.
主要成果:
- 慢性VNS导致较低的高亲和IgG标位和减少抗原特异性生殖中心 (GC) B细胞.
- 接受VNS治疗的GC B细胞显示出亡的增加和血细胞分化受损.
- 毛囊树突细胞 (FDC) 集群分散,它们的基因表达表明功能受损.
- 缺少产生乙胆的CD4+T细胞减弱了VNS诱导的变化.
- 在体外,α7和α9nAChR调节了B细胞中的TNF产生,而α4nAChR抑制了B细胞受体信号传递,影响了B细胞的存活率.
结论:
- 神经刺激会损害T-依赖B细胞的反应,导致抗体产生减少.
- 独特的尼古丁乙胆受体 (nAChRs) 介导VNS诱导的B细胞亡,分化和TNF产生.
- 由VNS引起的生殖中心形成和功能受损与乙胆信号通路有关.
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