The Role of NF-κB Signaling Pathway in Lacrimal Gland Damage in Primary Sjögren’s Syndrome: an in vivo study

Primary Sjögren’s syndrome (pSS) is an autoimmune disease characterized by inflammation and damage to exocrine glands, leading to symptoms such as dry eye and reduced tear production. The NF-κB signaling pathway plays a critical role in the inflammatory processes underlying pSS. The aims of the present in vivo study were to investigate the role of NF-κB signaling in lacrimal gland damage and tear secretion in the NOD/Ltj mouse, and to explore the therapeutic potential of NF-κB inhibition. The animal model was established using NOD/Ltj mouse and lacrimal gland pathological change was showed by H&E. Bioinformatics analysis was conducted through RNA sequencing (RNA-seq) and confirmed by RT-qPCR and Western blot. The NOD/Ltj mouse were treated with NF-κB inhibitor JSH-23. Tear secretion assays, ELISA, TUNEL staining, immunofluorescence, immunohistochemistry, and flow cytometry were employed to assess the role of NF-κB signaling in tear production, inflammatory cytokine expression, cell apoptosis, differentially expressed genes (DEGs), and cell differentiation in lacrimal gland damage in pSS mouse. NF-κB signaling was significantly activated in NOD/Ltj mouse lacrimal gland and pSS-related dry eye. NF-κB blockage decreased cell apoptosis, reduced inflammatory cytokine expression, and inhibited Th17 cell differentiation in NOD/Ltj mouse lacrimal glands, as well as restored tear production and normalized the expression of DEGs CARD14 and CCL19. NF-κB signaling played a pivotal role in lacrimal gland damage in pSS model NOD/Ltj mouse by involvement of cell apoptosis, inflammatory cytokine expression and Th17 cell differentiation. Targeting NF-κB signaling may offer a promising therapeutic approach for managing pSS-related dry eye.