NF‑κB signaling drives Th17‑mediated lacrimal gland injury and tear dysfunction in a murine model of primary Sjögren's syndrome

Primary Sjögren's syndrome (pSS) is a systemic autoimmune disorder characterized by chronic inflammation of exocrine glands, resulting in lacrimal gland dysfunction, reduced tear secretion and dry eye manifestations. The nuclear factor κB (NF‑κB) signaling pathway is a central regulator of inflammatory responses; however, its role in lacrimal gland injury in pSS remains incompletely defined. The present study investigated the contribution of NF‑κB signaling to lacrimal gland damage and tear secretion in non‑obese diabetic (NOD)/Ltj mice, an established in vivo model of pSS. Histopathological alterations were evaluated by hematoxylin and eosin staining. Transcriptomic profiling was performed using mRNA Sequencing and validated by western blotting analysis. Pharmacological inhibition of NF‑κB was achieved using JSH‑23. T helper 17 (Th17) cell differentiation, inflammatory cytokine production, Apoptosis and tear secretion were assessed by immunohistochemistry, flow cytometry, enzyme‑linked immunosorbent assay, terminal deoxynucleotidyl transferase dUTP nick end labeling staining and the phenol red thread test. NF‑κB signaling was markedly activated in the lacrimal glands of NOD/Ltj mice. Inhibition of NF‑κB reduced Th17 cell differentiation, decreased proinflammatory cytokine expression, attenuated Apoptosis, restored tear secretion and partially normalized the expression levels of differentially expressed genes, including CARD14 and CCL19 transcripts and their corresponding proteins, CARD14 and CCL19. These findings indicated that NF‑κB signaling contributes to Th17‑mediated lacrimal gland injury in pSS and suggested that pharmacological targeting of this pathway may represent a potential therapeutic strategy for pSS‑associated dry eye.