Review
Systematic evaluation of animal models for systemic sclerosis-associated interstitial lung disease: focus on pulmonary and extrapulmonary pathophysiology
S. Zhang1, Y. Wu2, Y. Li3, X. Ji4, Y. Huang5, W. Liu6, C. Tan7, Y. Luo8
- Department of Rheumatology and Immunology, and Laboratory of Rheumatology and Immunology, West China Hospital, Sichuan University, Chengdu, Sichuan; and Frontiers Science Center for Disease-related Molecular Network, West China, Hospital, Sichuan University, Chengdu, Sichuan, China.
- Department of Rheumatology and Immunology, and Laboratory of Rheumatology and Immunology, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
- Department of Rheumatology and Immunology, and Laboratory of Rheumatology and Immunology, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
- Department of Rheumatology and Immunology, and Laboratory of Rheumatology and Immunology, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
- Department of Rheumatology and Immunology, and Laboratory of Rheumatology and Immunology, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
- Department of Rheumatology and Immunology, and Laboratory of Rheumatology and Immunology, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
- Department of Rheumatology and Immunology, and Laboratory of Rheumatology and Immunology, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
- Department of Rheumatology and Immunology, and Laboratory of Rheumatology and Immunology, West China Hospital, Sichuan University, Chengdu, Sichuan; and Frontiers Science Center for Disease-related Molecular Network, West China, Hospital, Sichuan University, Chengdu, Sichuan, China. luoyubin2016@163.com
CER19602
Review
PMID: 43001850 [PubMed]
Received: 09/12/2025
Accepted : 29/04/2026
In Press: 05/11/2026
Abstract
Systemic sclerosis-associated interstitial lung disease (SSc-ILD) is a major driver of mortality in systemic sclerosis and a prototypical fibroinflammatory disorder in which pulmonary fibrosis unfolds alongside systemic immune, vascular and extrapulmonary abnormalities. Animal models remain essential for mechanistic interrogation and preclinical testing, yet most capture only selected facets of the disease and fall short of the integrated human phenotype. Here, we critically examine established SSc-ILD models through the lens of translational fidelity. Across bleomycinbased, chemical, genetic and immunemediated platforms, striking differences emerge in disease spectrum, reproducibility and biological relevance, and few models recapitulate the integrated fibroinflammatory, immune and vascular complexity of human SSc-ILD. This unresolved gap continues to constrain mechanistic insight and therapeutic development. Advancing the field will require next-generation models that more closely reflect the complexity, chronicity and heterogeneity of human SSc-ILD.
