单细胞转录组分析揭示了原发性Sjögren综合征中的免疫和树皮细胞异质性
Nan Xiang1, Hao Xu2, Zhou Zhou1
1Department of Rheumatology and Immunology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230001, China.
主要的Sjögren综合征涉及唾液腺中的免疫细胞变化. 研究人员发现了改变的B细胞和纤维细胞,为这种自身免疫性疾病提供了新的治疗点.
科学领域:
- 免疫学 免疫学 免疫学
- 细胞生物学 细胞生物学
- 自免疫性疾病 自免疫性疾病
背景情况:
- 主要Sjögren综合征 (pSS) 是一种影响外分泌腺体的自身免疫性疾病.
- 唾液腺 (SG) 功能障碍是PSS的一个标志,由淋巴细胞透驱动.
- 了解细胞异质性对于pSS的发病过程至关重要.
研究的目的:
- 用单细胞RNA测序研究pSS患者的唾液腺细胞异质性的研究.
- 确定与pSS.相关的特定细胞亚群和分子变化.
- 通过了解树皮-免疫相互作用来探索潜在的治疗点.
主要方法:
- 单细胞RNA测序 (scRNA-seq) 在来自11名pSS患者和5名对照患者的唾液腺组织上.
- 对细胞异质性,基因表达模式和细胞与细胞相互作用的分析.
- 伪素体轨迹分析以模拟B细胞分化的途径.
主要成果:
- 在pSS中的肌上皮细胞中降低SOX9的调节,与表皮再生受损有关.
- 在pSS中ACKR1+内皮细胞的扩张,可能有助于淋巴细胞迁移.
- 在pSS患者的SG中增加了外周血液中的IGHD+原始B细胞和独特的B细胞亚型 (VPREB3+,BANK1+,CD83+).
- 纤维细胞被确定为干细胞免疫网络的关键参与者,驱动炎症和组织损伤.
结论:
- scRNA-seq在pSS唾液腺中显示出显著的免疫和 stromal 细胞异质性.
- 特定的细胞亚群和分子变化为疾病机制提供了洞察力.
- 这些发现突出了针对pSS细胞相互作用和特定细胞类型的潜在治疗途径.
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