Academic Journal
Macrophage programming in systemic sclerosis: Niches, networks, and translational horizons.
| Τίτλος: | Macrophage programming in systemic sclerosis: Niches, networks, and translational horizons. |
|---|---|
| Συγγραφείς: | Luo H; Guangxi Medical University, Nanning, Guangxi, China. 202310072@sr.gxmu.edu.cn.; Department of Rheumatology and Immunology, The First Affiliated Hospital of University of South China, 69 Chuanshan Road, Hengyang, Hunan, 421001, China. 202310072@sr.gxmu.edu.cn., Hu D; Department of Neonatology, The First Affiliated Hospital of University of South China, Hengyang, Hunan, China. |
| Πηγή: | Seminars in immunopathology [Semin Immunopathol] 2026 Aug 27; Vol. 48 (1). Date of Electronic Publication: 2026 Aug 27. |
| Τύπος έκδοσης: | Journal Article; Review |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: Springer Country of Publication: Germany NLM ID: 101308769 Publication Model: Electronic Cited Medium: Internet ISSN: 1863-2300 (Electronic) Linking ISSN: 18632297 NLM ISO Abbreviation: Semin Immunopathol Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: Berlin : Springer |
| Ιατρικοί όροι (MeSH): | Scleroderma, Systemic*/metabolism , Scleroderma, Systemic*/etiology , Scleroderma, Systemic*/pathology , Scleroderma, Systemic*/therapy , Scleroderma, Systemic*/immunology , Macrophages*/metabolism , Macrophages*/immunology , Macrophage Activation*/immunology , Macrophage Activation*/genetics , Cell Plasticity*/genetics , Cell Plasticity*/immunology , Cellular Microenvironment*/immunology, Humans ; Animals ; Signal Transduction ; Translational Research, Biomedical ; Autoimmunity ; Disease Susceptibility ; Biomarkers ; Fibrosis |
| Περίληψη: | Systemic sclerosis (SSc) is a multisystem autoimmune disease characterized by immune dysregulation, microvascular injury, and progressive fibrosis. Among the immune populations implicated in SSc, macrophages are increasingly recognized as context-dependent participants in endothelial stress, inflammatory amplification, tissue remodeling, and fibroblast activation. Rather than relying on a static M1/M2 framework, recent studies support the view that macrophage-associated states are shaped by inducing cues, tissue niche, dominant effector function, and disease phase. In this review, we synthesize current evidence on macrophage-associated programs across vascular, dermal, and pulmonary compartments in SSc and discuss how these programs may help organize current understanding of the coupling between autoimmunity, vasculopathy, and fibrosis. We also highlight that recurrent signaling hubs-including JAK/STAT, TGF-β/SMAD, PDGF/PI3K/AKT/mTOR, Notch/Wnt, Hippo/YAP/TAZ, and metabolic regulators-reappear across macrophage-stromal crosstalk in SSc and related fibrotic settings. Importantly, we distinguish findings supported directly in human SSc from those derived from experimental systems or extrapolated from related fibrotic and autoimmune diseases, and we discuss biomarkers and therapeutic strategies according to their translational maturity. We propose that a macrophage-centered framework may be useful as an organizing and hypothesis-refining tool in SSc, but not as a validated disease-specific taxonomy or treatment algorithm. At present, many macrophage-centered biomarkers and therapeutic concepts remain insufficiently validated for routine clinical use, underscoring the need for stronger human tissue validation, clearer evidence calibration, and stage-aware translational studies. (© 2026. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.) |
| Competing Interests: | Declarations. Ethics approval: Not applicable. Generative AI disclosure: The author(s) declare that no Generative AI was used in the creation of this manuscript. Conference abstract disclosure: No related congress abstract has been published previously. Competing interests: The authors declare no competing interests. |
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| Contributed Indexing: | Keywords: Autoimmunity; Biomarkers; Fibrosis; Macrophages; Systemic sclerosis; Vasculopathy |
| Substance Nomenclature: | 0 (Biomarkers) |
| Entry Date(s): | Date Created: 20260827 Date Completed: 20260827 Latest Revision: 20261008 |
| Update Code: | 20261008 |
| DOI: | 10.1007/s00281-026-01084-x |
| PMID: | 42658262 |
| Βάση Δεδομένων: | MEDLINE |
| ISSN: | 1863-2300 |
|---|---|
| DOI: | 10.1007/s00281-026-01084-x |