Systemic sclerosis & Raynaud's
Endothelial IFI16 drives vasculopathy and profibrotic remodeling in systemic sclerosis by activating JAK/STAT signaling
Authors' conclusion
Collectively, endothelial IFI16 coupled IFN-I signaling to vasculopathy and fibrotic remodeling via JAK-STAT activation, highlighting IFI16 as a promising therapeutic target in SSc vasculopathy and the subsequent fibrosis.
Study context
- Population
- Systemic sclerosis (SSc) skin and endothelial cells
- Outcome
- IFI16 expression in SSc skin
Methodological detailsfunctional and pathway analyses in IFI16-overexpressing endothelial cells
- Functional and pathway analyses in IFI16-overexpressing endothelial cells
Main finding
As reported in the abstract
- IFI16 is significantly upregulated in SSc skin and ranks among the IFN-I-associated genes positively correlated with more severe skin fibrosis, shorter non-Raynaud disease duration, and elevated extracellular matrix deposition
Further findings
Cellular localisation of IFI16
- Enrichment of IFI16 in endothelial cells; co-localization of IFI16 with vasculature validated by immunofluorescence
- IFI16-high endothelial cells exhibited higher IFN activity and enhanced extracellular matrix remodeling
Cytokine stimulation of endothelial cells
- IL-6, IL-1β, TGF-β and IFN-⍺ upregulated IFI16 expression in endothelial cells
Gain-of-function experiments
- IFI16 overexpression impaired endothelial proliferation, migration, and tube formation, while driving the transition of endothelial cells towards mesenchymal cells through JAK-STAT signaling
- Inhibition of JAK-STAT signaling reversed IFI16-induced endothelial-mesenchymal transition
Original publication
Endothelial IFI16 drives vasculopathy and profibrotic remodeling in systemic sclerosis by activating JAK/STAT signaling. Rheumatology (Oxford). Published 12 November 2026. doi:10.
Composed by AI from the published abstract and checked against it. How Briefs are made →