Single-cell transcriptome profiling reveals immune and stromal cell heterogeneity in primary Sjögren’s syndrome

• Published in: iScience Vol. 26; no. 10; p. 107943
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 20.10.2023; Elsevier
• Subjects: Cell biology; Molecular biology; Transcriptomics; Cell biology; Molecular biology; Transcriptomics
• ISSN: 2589-0042; 2589-0042
• DOI: 10.1016/j.isci.2023.107943

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. [Display omitted] •Elevated ACKR1+ endothelial cells in pSS may promote transendothelial migration•SOX9 plays a vital role in epithelial cell regeneration and differentiation in pSS•Heterogeneity of B and CD4+ T cells in peripheral blood and salivary glands of pSS•Fibroblast subsets are pivotal for cell-cell interactions in pSS salivary glands Molecular biology; Cell biology; Transcriptomics