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Background: Tissue-resident fibroblasts have emerged as a key cell type controlling the local tissue microenvironment in chronic and inflammatory diseases. The specific contribution of fibroblasts in the pathogenesis of Sjögren's syndrome (SjS) remains incompletely understood. Objectives: To characterize the inflammatory response of cultured human salivary gland-derived fibroblasts (SGF) from patients with SjS. Methods: SGF were cultured form enzymatically digested minor salivary gland biopsies of patients with suspected SjS, including samples of patients with SjS and controls (sicca symptoms) that do not fulfil the SjS classification criteria. SGF were characterized by FACS analysis for the presence of fibroblast markers (CD90, PDPN) and the absence of epithelial (EPCAM) and lymphocyte (CD45) markers. SGF were treated with IL-1 (1 ng/µl) for 24h. Transcriptomes were analysed by RNA-sequencing (n=3/ group; Illumina NovaSeq 6000). Pathway enrichment analysis was conducted using Gene Onthology and Gene Set Enrichment Analysis (GSEA). Levels of cytokines and chemokines (BAFF, CLL2, CCL5, CX3CL1, CXCL10, IL6, IL8) in cell cultured supernatants were measured by ELISA. Proliferation of SGF was assessed by BrdU assay. Results: SGF cultures (n=6) were positive for CD90 and PDPN and negative for EPCAM and CD45. SGF from patients with SjS (n=7) exhibited increased proliferation rates compared to SGF from sicca controls (n=5; p 1.5, FDRConclusion: Our data point to an intrinsic activation of SjS SGF compared to control SGF, characterized by increased proliferation and differences in their transcriptomes in response to stimulation with IL-1. Local SGF activity in SjS may promote the vicious circle of chronic inflammation in salivary glands. REFERENCES: NIL. Acknowledgements: NIL. Disclosure of Interests: Kerstin Klein: None declared, Ondrej Pastva: None declared, Matthias Brunner: None declared, Daniel Guggisberg: None declared, Marco Kreuzer: None declared, Larissa Moser: None declared, Marco Sprecher: None declared, Muriel Elhai: None declared, Rémy Bruggmann: None declared, Britta Maurer Boehringer-Ingelheim, GSK, Novartis, Otsuka, MSD, Novartis, Boehringer Ingelheim, Jannsen-Cilag, GSK, Novartis.
Pastva et al. (Sat,) studied this question.