Tree shrews as a new animal model for systemic sclerosis research

Area of Science:

• Biomedical Research
• Animal Models
• Translational Medicine

Background:

• Systemic sclerosis (SSc) is a chronic, debilitating autoimmune disease with no effective treatments.
• Current animal models have limitations in fully recapitulating human SSc pathology.
• Tree shrews offer unique genetic and immunological similarities to humans, making them suitable for SSc research.

Purpose of the Study:

• To establish and validate a tree shrew model for systemic sclerosis (SSc).
• To investigate the molecular and immunological characteristics of this novel SSc model.
• To assess the potential of the tree shrew model for SSc translational research.

Main Methods:

• Induction of SSc in tree shrews via subcutaneous bleomycin injections over 21 days.
• Assessment of skin and organ fibrosis, inflammation, and autoantibody production.
• RNA sequencing and bioinformatics analysis of skin transcriptome, including differential gene expression and immune cell infiltration.

Main Results:

• Bleomycin successfully induced SSc-like phenotypes, including skin and lung fibrosis, and autoantibodies.
• RNA sequencing identified 90 differentially expressed genes enriched in SSc-relevant pathways (e.g., PPAR signaling, ECM interactions).
• Analysis revealed 20 infiltrating immune cell types and identified 10 highly conserved hub genes associated with SSc pathology.

Conclusions:

• The tree shrew model effectively mimics key aspects of human systemic sclerosis.
• This validated model provides a novel platform for studying SSc pathogenesis.
• The tree shrew SSc model holds significant promise for advancing translational research in SSc.