ArticleAnnals of the rheumatic diseases2024
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.
Article in Annals of the rheumatic diseases, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 1 of them a synthesis that pooled it.
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Who cites it
18 citing papers in PubMed, 1 synthesis or guideline pooled it, 32 citations in OpenAlex.
- TIR domain proteins: regulatory mechanisms in the tumor immune microenvironment, clinical translation strategies, and prospects for precision therapy applications.Frontiers in immunology · 2025Pooled it
- Hdac11 promotes idiopathic pulmonary fibrosis through macrophage M2-type polarization and myofibroblast accumulation by inhibiting Parkin-dependent mitophagy.Nature communications · 2026Article
- Peripheral lncRNA-IL1RAP Dysregulation in Schizophrenia: A Multi-Omics Bridge Between Immunity and Diagnosis.Brain and behavior · 2026Article
- Complement protein C1q induces endothelial apoptosis through C1qBP regulation of mitochondrial function in lung endothelial cells in systemic sclerosis.Molecular medicine (Cambridge, Mass.) · 2026Article
- [Effect of interleukin-33 on glucocorticoid-induced osteonecrosis of the femoral head in mice].Zhongguo xiu fu chong jian wai ke za zhi = Zhongguo xiufu chongjian waike zazhi = Chinese journal of reparative and reconstructive surgery · 2026Article
- The IL-36 Cytokine Rheostat: Hierarchical Regulation of Epithelial-Immune Crosstalk and Precision Therapy in Psoriatic and Related Dermatoses.Clinical, cosmetic and investigational dermatology · 2026Review
- Emerging therapies for the treatment of systemic sclerosis.Nature reviews. Rheumatology · 2025Review
- Neutrophil membrane-camouflaged SiRNA nanoplatform targeting IL-33 attenuates osteoarthritis through autophagy-dependent senescence regulation.Journal of nanobiotechnology · 2025Article
- Antifibrotic effects of specific targeting of the 5-hydroxytryptamine 2B receptor (5-HTArthritis & rheumatology (Hoboken, N.J.) · 2025Article
- Safety, tolerability, and preliminary efficacy of nadunolimab, an anti-IL- 1 receptor accessory protein monoclonal antibody, in combination with pembrolizumab in patients with solid tumors.Investigational new drugs · 2025Article
- IL1RAP Expression in Human Atherosclerosis: A Target of Novel Antibodies to Reduce Vascular Inflammation and Adhesion.Journal of the American Heart Association · 2025Article
- An international perspective on the future of systemic sclerosis research.Nature reviews. Rheumatology · 2025Review
- Advances in understanding the role of interleukins in pulmonary fibrosis (Review).Experimental and therapeutic medicine · 2025Review
- Integrated single-cell and transcriptome sequencing data reveal the value of IL1RAP in gastric cancer microenvironment and prognosis.Frontiers in oncology · 2025Article
- Keloids and inflammation: the crucial role of IL-33 in epidermal changes.Frontiers in immunology · 2025Article
- Characterization of Endothelial Cell Subclusters in Localized Scleroderma Skin with Single-Cell RNA Sequencing Identifies NOTCH Signaling Pathway.International journal of molecular sciences · 2024Article
- Single-cell mass cytometry in immunological skin diseases.Frontiers in immunology · 2024Review
- Dihydromyricetin improving myocardial function in the mice induced by CClInternational journal of immunopathology and pharmacologyArticle
Corrections and comments
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Authors and funding
16 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe interleukin (IL)-1 receptor accessory protein (IL1RAP) is an essential coreceptor required for signalling through the IL-1, IL-33 and IL-36 receptors. Here, we investigate the antifibrotic potential of the combined inhibition of these cytokines by an anti-IL1RAP antibody to provide a scientific background for clinical development in systemic sclerosis (SSc).
methodsThe expression of IL1RAP-associated signalling molecules was determined by data mining of publicly available RNA sequencing (RNAseq) data as well as by imaging mass cytometry. The efficacy of therapeutic dosing of anti-IL1RAP antibodies was determined in three complementary mouse models: sclerodermatous chronic graft-versus-host disease (cGvHD), bleomycin-induced dermal fibrosis model and topoisomerase-I (topo)-induced fibrosis.
resultsSSc skin showed upregulation of IL1RAP and IL1RAP-related signalling molecules on mRNA and protein level compared with normal skin. IL-1, IL-33 and IL-36 all regulate distinct gene sets related to different pathophysiological processes in SSc. The responses of human fibroblasts and endothelial cells to IL-1, IL-33 and IL-36 were completely blocked by treatment with an anti-IL1RAP antibody in vitro. Moreover, anti-IL1RAP antibody treatment reduced dermal and pulmonary fibrosis in cGvHD-induced, bleomycin-induced and topoisomerase-induced fibrosis. Importantly, RNAseq analyses revealed effects of IL1RAP inhibition on multiple processes related to inflammation and fibrosis that are also deregulated in human SSc skin.
conclusionThis study provides the first evidence for the therapeutic benefits of targeting IL1RAP in SSc. Our findings have high translational potential as the anti-IL1RAP antibody CAN10 has recently entered a phase one clinical trial.
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