Transcriptomic profiling of scleroderma monocytes reveals links with cardiovascular complications, implicating Notch...

Area of Science:

• Immunology
• Genomics
• Cardiology

Background:

• Monocytes and macrophages are key drivers of inflammation and fibrosis in systemic sclerosis.
• Understanding monocyte gene expression is crucial for identifying systemic sclerosis complications and therapeutic targets.

Purpose of the Study:

• To investigate gene expression profiles of monocytes in systemic sclerosis patients.
• To explore the relationship between these profiles and disease complications.
• To identify novel therapeutic targets for systemic sclerosis.

Main Methods:

• Bulk RNA sequencing was performed on monocytes from 48 systemic sclerosis patients and 15 controls.
• Differential gene expression, hierarchical clustering, and pathway analysis were conducted.
• Interferon signature score (IFN6) and correlations with clinical features, including global longitudinal strain (GLS), were analyzed.

Main Results:

• Four monocyte gene expression subgroups were identified: two inflammatory and two non-inflammatory.
• Inflammatory subgroups showed high interferon-related gene expression and were associated with pulmonary hypertension and cardiac involvement.
• Elevated IFN6 correlated significantly with impaired GLS, and Notch signaling was enriched in genes linked to cardiac dysfunction.

Conclusions:

• A mechanistic link between interferon activity, Notch signaling, and cardiac complications in systemic sclerosis is proposed.
• These findings offer new insights into systemic sclerosis pathogenesis.
• Potential novel therapeutic targets for systemic sclerosis have been identified.