ArticleArthritis & rheumatology (Hoboken, N.J.)2020
Profibrotic Activation of Human Macrophages in Systemic Sclerosis.
Article in Arthritis & rheumatology (Hoboken, N.J.), 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
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Who cites it
51 citing papers in PubMed, 85 citations in OpenAlex.
- Mycophenolate mofetil directly modulates myeloid viability and pro-fibrotic activation of human macrophages.Rheumatology (Oxford, England) · 2025Trial
- Noncoding RNA TY1 reverses fibrosis in systemic sclerosis by attenuating the cGAS/STING pathway.JCI insight · 2026Article
- Mechanisms of fibrotic tissue remodelling: insights from systemic sclerosis.Nature reviews. Rheumatology · 2026Review
- Crosstalk between macrophages and fibroblasts contributes to inflammation and damage in giant cell arteritis.Rheumatology (Oxford, England) · 2026Article
- Multimodal analyses of early, untreated systemic sclerosis skin identify a proinflammatory vascular niche of macrophage-fibroblast signaling.JCI insight · 2026Article
- Anti-CD19 CAR T-cell therapy for autoimmune diseases: from exploratory clinical trials to quantitative pharmacodynamic modeling development.Frontiers in immunology · 2026Review
- Systemic sclerosis: pathogenic mechanisms and their implications for treatment.Seminars in immunopathology · 2025Review
- Red light promotes dermis-epidermis remodeling via TGFβ and AKT-mediated collagen dynamics in naturally aging mice.Zoological research · 2025Article
- Dynamic macrophage phenotypes in autoimmune and inflammatory rheumatic diseases.Nature reviews. Rheumatology · 2025Review
- T Cells Enhance Tissue Complexity and Function to Study Fibrosis in 3D Skin-Like Tissue Models.Tissue engineering. Part C, Methods · 2025Article
- [Pharmacological inhibition of fibrosis exemplified by systemic sclerosis : Possibilities and limits].Innere Medizin (Heidelberg, Germany) · 2025Article
- M2 macrophage co-culture overrides viscoelastic hydrogel mechanics to promote IL6-dependent fibroblast activation.Cell biomaterials · 2025Article
- An international perspective on the future of systemic sclerosis research.Nature reviews. Rheumatology · 2025Review
- The Multifaceted Role of Macrophages in Biology and Diseases.International journal of molecular sciences · 2025Review
- Development of immunocompetent full thickness skin tissue constructs to model skin fibrosis for high-throughput drug screening.Biofabrication · 2024Article
- Article
- Direct M2 macrophage co-culture overrides viscoelastic hydrogel mechanics to promote fibroblast activation.bioRxiv : the preprint server for biology · 2024Article
- Systemic Sclerosis-Associated Pulmonary Arterial Hypertension: From Bedside to Bench and Back Again.International journal of molecular sciences · 2024Review
- Nintedanib downregulates the profibrotic M2 phenotype in cultured monocyte-derived macrophages obtained from systemic sclerosis patients affected by interstitial lung disease.Arthritis research & therapy · 2024Article
- Development and validation of a new diagnostic prediction model of ENHO and NOX4 for early diagnosis of systemic sclerosis.Frontiers in immunology · 2024Article
Corrections and comments
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Authors and funding
14 authors at 3 institutions in 1 country.
Funding
Abstract
objectiveGenome-wide gene expression studies implicate macrophages as mediators of fibrosis in systemic sclerosis (SSc), but little is known about how these cells contribute to fibrotic activation in SSc. We undertook this study to characterize the activation profile of SSc monocyte-derived macrophages and assessed their interaction with SSc fibroblasts.
methodsPlasma and peripheral blood mononuclear cells (PBMCs) were obtained from whole blood from SSc patients (n = 24) and age- and sex-matched healthy controls (n = 12). Monocytes were cultured with autologous or allogeneic plasma to differentiate cells into macrophages. For reciprocal activation studies, macrophages were cocultured with fibroblasts using Transwell plates.
resultsThe gene expression signature associated with blood-derived human SSc macrophages was enriched in SSc skin in an independent cohort and correlated with skin fibrosis. SSc macrophages expressed surface markers associated with activation and released CCL2, interleukin-6, and transforming growth factor β under basal conditions (n = 8) (P < 0.05). Differentiation of healthy donor monocytes in plasma from SSc patients conferred the immunophenotype of SSc macrophages (n = 13) (P < 0.05). Transwell experiments demonstrated that coculture of SSc macrophages with SSc fibroblasts induced fibroblast activation (n = 3) (P < 0.05).
conclusionThese data demonstrate that the activation profile of SSc macrophages is profibrotic. SSc macrophages are activated under basal conditions and release mediators and express surface markers associated with both alternative and inflammatory macrophage activation. These findings also suggest that activation of SSc macrophages arises from soluble factors in local microenvironments. These studies implicate macrophages as likely drivers of fibrosis in SSc and suggest that therapeutic targeting of these cells may be beneficial in ameliorating disease in SSc patients.
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