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

Nan Xiang,Hao Xu,Zhou Zhou,Junyu Wang,Pengfei Cai,Li Wang,Zhen Tan,Yingbo Zhou,Tianping Zhang,Jiayuan Zhou,Ke Liu,Songwen Luo,Minghao Fang,Guosheng Wang,Zhuo Chen,Chuang Guo,Xiaomei Li

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.