ArticleAnnals of the rheumatic diseases2025
Human hypofunctional NCF1 variants promote pulmonary fibrosis in the bleomycin-induced mouse model and patients with systemic sclerosis via expansion of SPP1
Article in Annals of the rheumatic diseases, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed.
- Beyond polarization: a receptor-centered framework for macrophage function and therapy in skin diseases.Clinical and experimental medicine · 2026Review
- SPP1+ macrophages contribute to silica-induced pulmonary inflammation and fibrosis via the ERK/JNK signaling pathway.American journal of respiratory cell and molecular biology · 2026Article
- 2025 annual review of basic and translational research advances in pulmonary fibrosis: a narrative review.Journal of thoracic disease · 2026Review
- Neutrophil reprogramming underlie vasculopathy and lung disease in systemic sclerosis.Cell death & disease · 2026Article
- Mechanisms of fibrotic tissue remodelling: insights from systemic sclerosis.Nature reviews. Rheumatology · 2026Review
- Monocyte-mediated mechanisms in idiopathic pulmonary fibrosis: opportunities for early intervention.Apoptosis : an international journal on programmed cell death · 2026Review
- The pro-fibrogenic role of SPP1Frontiers in immunology · 2026Review
- Common biomarkers of idiopathic pulmonary fibrosis and systemic sclerosis based on WGCNA and machine learning.Scientific reports · 2025Article
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Authors and funding
17 authors.
Funding
Abstract
objectiveWe assessed the role of a systemic lupus erythematosus causal hypofunctional variant, neutrophil cytosolic factor 1 (NCF1)-p.Arg90His (p.R90H) substitution, in systemic sclerosis (SSc).
methodsAssociation of NCF1-H90 with SSc was performed in case-control cohorts, bleomycin (BLM)-treated Ncf1-R90 C57BL/6 wildtype and Ncf1-H90 knock-in (KI) littermates. Peripheral blood mononuclear cell (PBMC) subsets were analysed by cytometry by time-of-flight.
resultsThe NCF1-H90 allele is associated with risk for diffuse cutaneous SSc (dcSSc) in Chinese and European Americans, and lung fibrosis in Chinese patients with SSc (OR=2.09, p=7.96E-10). Low copy number of NCF1 associated with lung fibrosis in European Americans (OR=4.33, p=2.60E-2). BLM-treated KI mice demonstrated increased pulmonary fibrosis, exhibiting activated type I interferon signature, elevated Spp1, Ccl2, Arg1, Timp1 and Il6 expression, enriched macrophage scores in lung tissues. In a longitudinal observation cohort, homozygous H90 patients with SSc at baseline had increased anti-nuclear antibody titres, anti-topoisomerase antibody seropositivity and anti-centromere antibody seronegativity, increased incidence of lung fibrosis and Gender-Age-lung Physiology index, elevated modified Rodnan Skin Score (mRSS) and elevated plasma osteopontin (OPN, SPP1), CCL2, ARG1, TIMP-1 and IL-6. These H90 patients with SSc sustained elevated mRSS during follow-up years with decreased survival. The 0, 1 and 2 copies of H90 carriage in SSc PBMCs exhibited dose-dependent increases in profibrotic CD14
conclusionLow NCF1 activity increases the risk for the development of dcSSc and lung fibrosis via expanding profibrotic SPP1
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