Systemic sclerosis & Raynaud's
DNA from macrophages induces fibrosis and vasculopathy through POLR3A/stimulator of IFN genes (STING)/type I interferon axis in systemic sclerosis
Authors' conclusion
SSc presented increased DNA leakage and STING pathway activation. DNA from macrophages induced type I IFN signature of fibroblasts and ECs through POLR3A/STING pathway.
Study context
- Population
- SSc patients (skin, serum); SSc fibroblasts and human umbilical vein endothelial cells (HUVECs) transfected with macrophage DNA; Bleomycin (BLM)-induced SSc mice
- Outcome
- Role of POLR3A/STING/type I IFN in SSc
Methodological detailsin vitro, animal model (BLM-induced SSc mice)
- In vitro
- Animal model (BLM-induced SSc mice)
Main finding
As reported in the abstract
- Cytosolic DNA, colocalization of STING with α-SMA or CD31 in skin, and STING pathway in serum increased in SSc patients
- Macrophage-derived DNA stimulated translocation of POLR3A from nucleus to perinuclear region near STING and activated POLR3A/STING/type I IFN response, monocyte adhesion and MCP-1 expression in fibroblasts/HUVECs and collagen overproduction of fibroblasts
- Activated IRF3 bound to the MCP-1 promoter
- STING deficiency or H151 ameliorated fibrosis and vasculopathy in vitro and in BLM-induced SSc mice
Original publication
DNA from macrophages induces fibrosis and vasculopathy through POLR3A/STING/type I interferon axis in systemic sclerosis. Rheumatology (Oxford). Published 10 June 2022. doi:10.
Composed by AI from the published abstract and checked against it. How Briefs are made →