Xiang Nan, Xu Hao, Zhou Zhou, Wang Junyu, Cai Pengfei, Wang Li, Tan Zhen, Zhou Yingbo, Zhang Tianping, Zhou Jiayuan, Liu Ke, Luo Songwen, Fang Minghao, Wang Guosheng, Chen Zhuo, Guo Chuang, Li Xiaomei
Department 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.
Division of Molecular Medicine, Hefei National Laboratory for Physical Sciences at Microscale, School of Basic Medical Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230021, China.
iScience. 2023 Sep 16;26(10):107943. doi: 10.1016/j.isci.2023.107943. eCollection 2023 Oct 20.
Primary Sjögren's syndrome (pSS) is a complex autoimmune disease characterized by lymphocytic infiltration and exocrine dysfunction, particularly affecting the salivary gland (SG). We employed single-cell RNA sequencing to investigate cellular heterogeneity in 11 patients with pSS and 5 non-SS controls. Notably, patients with pSS exhibited downregulated SOX9 in myoepithelial cells, potentially associated with impaired epithelial regeneration. An expanded ACKR1 endothelial subpopulation in patients with pSS suggested a role in facilitating lymphocyte transendothelial migration. Our analysis of immune cells revealed expanded IGHD naive B cells in peripheral blood from patients with pSS. Pseudotime trajectory analysis outlined a bifurcated differentiation pathway for peripheral B cells, enriching three subtypes (VPREB3 B, BANK1 B, CD83 B cells) within SGs in patients with pSS. Fibroblasts emerged as pivotal components in a stromal-immune interaction network, potentially driving extracellular matrix disruption, epithelial regeneration impairment, and inflammation. Our study illuminates immune and stromal cell heterogeneity in patients with pSS, offering insights into therapeutic strategies.
原发性干燥综合征（pSS）是一种复杂的自身免疫性疾病，其特征为淋巴细胞浸润和外分泌功能障碍，尤其会影响唾液腺（SG）。我们采用单细胞RNA测序技术研究了11例pSS患者和5例非干燥综合征（non-SS）对照的细胞异质性。值得注意的是，pSS患者的肌上皮细胞中SOX9表达下调，这可能与上皮再生受损有关。pSS患者中一种扩增的ACKR1内皮细胞亚群表明其在促进淋巴细胞跨内皮迁移中发挥作用。我们对免疫细胞的分析显示，pSS患者外周血中IGHD初始B细胞扩增。伪时间轨迹分析勾勒出外周B细胞的一种分叉分化途径，在pSS患者的唾液腺中富集了三种亚型（VPREB3 B细胞、BANK1 B细胞、CD83 B细胞）。成纤维细胞成为基质-免疫相互作用网络中的关键组成部分，可能导致细胞外基质破坏、上皮再生受损和炎症。我们的研究阐明了pSS患者的免疫和基质细胞异质性，为治疗策略提供了见解。
