Objective:

To evaluate the NOD/ShiLtJ mouse model for salivary gland fibrosis in the context of Sjögren's disease and assess the impact of antifibrotic therapy on extracellular matrix remodeling.

Approach:

• Model Evaluation: Utilized the NOD/ShiLtJ mouse model to study salivary gland fibrosis associated with Sjögren's disease.
• Therapeutic Assessment: Administered nintedanib, an FDA-approved antifibrotic agent, to evaluate its effects on fibrosis in the context of Sjögren's disease.
• Fibrosis Assessment: Employed single-cell RNA sequencing to identify ECM gene expression, Picrosirius red staining, and AI-assisted digital pathology for quantification of collagen I.

Key Findings:

• Fibroblast populations in NOD/ShiLtJ mice showed increased expression of ECM genes, including Col1a1, Col1a2, and Col3a1, compared to controls.
• Significant fibrotic remodeling was observed in the periacinar ECM of submandibular glands.
• Fibrosis severity correlated with the diabetic phenotype and progressed with age.
• Nintedanib treatment resulted in modest reductions in multiple fibrotic indices.

Interpretation:

The NOD/ShiLtJ mouse model demonstrates characteristics of SjD-associated salivary gland fibrosis, supporting antifibrotic strategies as a potential therapeutic approach.

Limitations:

• The study primarily focuses on a mouse model, which may not fully replicate the complexities of human Sjögren's disease.
• The effects of nintedanib were modest and may require further investigation to establish clinical relevance.

Conclusion:

The findings provide evidence supporting the exploration of antifibrotic therapies for salivary gland dysfunction in Sjögren's disease.