Fibrotic remodeling in the NOD/ShiLtJ mouse model of Sjögren’s disease: insights from single-cell transcriptomics and AI-driven ECM quantification - Report - MDSpire

Exploring Fibrotic Changes in the NOD/ShiLtJ Mouse Model of Sjögren’s Disease: Insights from Single-Cell Transcriptomics and AI-Enhanced ECM Analysis

  • By

  • Jennifer M. Morrissey

  • Deirdre A. Nelson

  • Li Chen

  • Mathieu Petitjean

  • Joey R. Tavarez

  • Amber L. Altrieth-Flagg

  • Nicholas L. Moskwa

  • Renae Williams-Atkinson

  • Ben Fowler

  • Rafael Pena

  • Kennedi Weston

  • Nikhita Kumar

  • Nathan Aist

  • Melinda Larsen

  • July 20, 2026

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Clinical Report: Exploring Fibrotic Changes in the NOD/ShiLtJ Mouse Model of Sjögren’s Disease

Overview

This study investigates the role of fibrosis in Sjögren's Disease using the NOD/ShiLtJ mouse model.

Background

Sjögren's Disease (SjD) is an autoimmune disorder that significantly impacts quality of life through symptoms such as dry mouth and dry eyes. Understanding the mechanisms of fibrosis in SjD is crucial, as fibrosis contributes to glandular dysfunction and is less understood compared to inflammation. The NOD/ShiLtJ mouse model provides a valuable platform for studying these fibrotic changes.

Data Highlights

MeasurementControl MiceNOD/ShiLtJ Mice
Col1a1 LevelsBaselineIncreased
Col1a2 LevelsBaselineIncreased
Col3a1 LevelsBaselineIncreased
Fibrosis SeverityLowHigh
Nintedanib Treatment EffectNoneModest Reduction

Key Findings

  • Fibroblast populations in NOD/ShiLtJ mice showed increased ECM gene expression compared to controls.
  • Significant fibrotic remodeling was observed in the periacinar ECM of salivary glands.
  • Fibrosis severity correlated with the diabetic phenotype of the NOD/ShiLtJ strain.
  • Both periductal and periacinar fibrosis progressed with age in these mice.
  • Nintedanib treatment resulted in modest reductions in multiple fibrotic indices over 8 weeks.

Clinical Implications

Further research is needed to explore the long-term effects and clinical applicability of antifibrotic treatments in Sjögren's Disease.

Conclusion

This study establishes the NOD/ShiLtJ mouse model as a relevant system for studying SjD-associated fibrosis.

Related Resources & Content

  1. Frontiers in Immunology, 2026 -- Development of an improved preclinical humanized mouse platform representing the diverse clinical phenotypes of Sjögren’s syndrome
  2. Arthritis & Rheumatology, 2026 -- Distinct Molecular Pathways Supporting Sjögren Disease Clusters and Disease Progression
  3. npj Digital Medicine, 2026 -- Combining Multi-Omics Approaches with Machine Learning to Unravel Cellular Diversity and Fibrotic Regulatory Pathways in the Transition from MASLD to MASH
  4. Frontiers in Immunology, 2026 -- Spatial transcriptomics reveals an SPP1-centered immune–fibrotic axis associated with fibrosis-related tissue remodeling in IgG4-related disease
  5. PMC, 2016 -- 2016 ACR-EULAR Classification Criteria for primary Sjögren’s Syndrome: A Consensus and Data-Driven Methodology Involving Three International Patient Cohorts
  6. PMC, 2023 -- Idiopathic Pulmonary Fibrosis (an Update) and Progressive Pulmonary Fibrosis in Adults: An Official ATS/ERS/JRS/ALAT Clinical Practice Guideline
  7. PubMed, 2023 -- Safety and Efficacy of Ianalumab in Patients With Sjögren's Disease: 52-Week Results From a Randomized, Placebo-Controlled, Phase 2b Dose-Ranging Study
  8. 2016 ACR-EULAR Classification Criteria for primary Sjögren’s Syndrome: A Consensus and Data-Driven Methodology Involving Three International Patient Cohorts - PMC
  9. Idiopathic Pulmonary Fibrosis (an Update) and Progressive Pulmonary Fibrosis in Adults: An Official ATS/ERS/JRS/ALAT Clinical Practice Guideline - PMC
  10. Safety and Efficacy of Ianalumab in Patients With Sjögren's Disease: 52-Week Results From a Randomized, Placebo-Controlled, Phase 2b Dose-Ranging Study - PubMed

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