Systemic sclerosis & Raynaud's
Combined inhibition of IL-1, IL-33 and IL-36 signalling by targeting IL1RAP ameliorates skin and lung fibrosis in preclinical models of systemic sclerosis
Authors' conclusion
This study provides the first evidence for the therapeutic benefits of targeting IL1RAP in SSc.
Study context
- Population
- Systemic sclerosis (SSc) skin (public RNA sequencing (RNAseq) data, imaging mass cytometry); human fibroblasts and endothelial cells in vitro; mouse models of sclerodermatous chronic graft-versus-host disease (cGvHD), bleomycin-induced dermal fibrosis and topoisomerase-I-induced fibrosis
- Comparison
- Anti-IL1RAP antibody in preclinical models of SSc
Methodological detailspreclinical, three complementary mouse models, RNAseq data mining, imaging mass cytometry
- Preclinical
- Three complementary mouse models
- RNAseq data mining
- Imaging mass cytometry
Main finding
As reported in the abstract
- SSc skin: upregulation of IL1RAP and IL1RAP-related signalling molecules on mRNA and protein level vs normal skin
- IL-1, IL-33 and IL-36 each regulate distinct gene sets related to different pathophysiological processes in SSc
- Responses of human fibroblasts and endothelial cells to IL-1, IL-33 and IL-36 completely blocked by anti-IL1RAP antibody in vitro
- Anti-IL1RAP antibody reduced dermal and pulmonary fibrosis in cGvHD-, bleomycin- and topoisomerase-induced fibrosis
- RNAseq: IL1RAP inhibition affected multiple inflammation- and fibrosis-related processes also deregulated in human SSc skin
Original publication
Combined inhibition of IL-1, IL-33 and IL-36 signalling by targeting IL1RAP ameliorates skin and lung fibrosis in preclinical models of systemic sclerosis. Ann Rheum Dis. Published 27 August 2024. doi:10.
Composed by AI from the published abstract and checked against it. How Briefs are made →