ArticleScience immunology2022
Epiregulin is a dendritic cell-derived EGFR ligand that maintains skin and lung fibrosis.
Article in Science immunology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 54 citations in OpenAlex.
- Epiregulin Mitigates Type 2 Diabetes-associated Cognitive Dysfunction by Inhibiting Hippocampal Neuronal Ferroptosis via the Nrf2 Pathway.Molecular neurobiology · 2026Article
- Interfollicular communication among preovulatory follicles after luteinizing hormone signaling.Endocrinology · 2026Article
- Myeloid infiltration and epidermal dysregulation characterize cutaneous photosensitivity in systemic lupus erythematosus.Science translational medicine · 2026Article
- Quiescent tumor cells shape the immunosuppressive microenvironment in pancreatic cancer.Nature communications · 2026Article
- Clonal lineage tracing of innate immune cells in human cancer.Cancer cell · 2026Article
- ANGPTL4 contributes to osimertinib resistance through NDRG1-associated extracellular matrix remodeling in EGFR-mutant NSCLC organoid models.Cancer cell international · 2026Article
- scRNA-seq and genomics analyses reveal key mechanisms of inverted papilloma-associated sinonasal squamous cell carcinoma malignant transformation.bioRxiv : the preprint server for biology · 2026Article
- Single nuclei/cell transcriptomics reveal DMD driven cell dynamics and mechanisms of fibroblast inflammatory tissue priming in human dystrophic muscle.Research square · 2026Article
- Multifaceted regulation of immune cells in radiation-induced pulmonary fibrosis: from mechanistic insights to targeted therapies.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Review
- SUN2 mediates epigenetic remodeling to drive mechanotransduction during skin fibrosis.bioRxiv : the preprint server for biology · 2026Article
- Decoding organ fibrosis: mechanistic insights and emerging therapeutic strategies.Signal transduction and targeted therapy · 2026Review
- Mendelian Randomization Reveals Genetic Associations Between Immune Traits and Urethral Stricture.Mediators of inflammation · 2026Article
- Immune-Mediated Gut-Lung Axis in IPF: Bidirectional Mendelian Randomization and Mediation Analysis of Microbiota, Inflammatory Proteins, and Metabolites.Endocrine, metabolic & immune disorders drug targets · 2026Article
- The TREM2 paradox in fibrosis: a unified mechanism for opposite outcomes across organs.Frontiers in immunology · 2026Review
- Harnessing Phase Separation in the Extracellular Matrix: From Mechanisms to Therapeutic Opportunities.BioMed research international · 2026Review
- Integrating mechanical cues inFrontiers in immunology · 2026Review
- Article
- N-phenylquinazolin-4-amine-based EGFR TKIs suppress pulmonary fibrosis by modulating the EGFR/ERBB3 axis in epithelial-macrophage interaction.Communications biology · 2025Article
- Role of oxygen sensing and hypoxia-inducible factors in orchestrating innate immune responses.Nature immunology · 2025Review
- The spatial and temporal activation of macrophages during fibrosis.Nature reviews. Immunology · 2025Review
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10 authors at 3 institutions in 1 country.
Funding
Abstract
Immune cells are fundamental regulators of extracellular matrix (ECM) production by fibroblasts and have important roles in determining extent of fibrosis in response to inflammation. Although much is known about fibroblast signaling in fibrosis, the molecular signals between immune cells and fibroblasts that drive its persistence are poorly understood. We therefore analyzed skin and lung samples of patients with diffuse cutaneous systemic sclerosis, an autoimmune disease that causes debilitating fibrosis of the skin and internal organs. Here, we define a critical role of epiregulin-EGFR signaling between dendritic cells and fibroblasts to maintain elevated ECM production and accumulation in fibrotic tissue. We found that epiregulin expression marks an inducible state of DC3 dendritic cells triggered by type I interferon and that DC3-derived epiregulin activates EGFR on fibroblasts, driving a positive feedback loop through NOTCH signaling. In mouse models of skin and lung fibrosis, epiregulin was essential for persistence of fibrosis in both tissues, which could be abrogated by epiregulin genetic deficiency or a neutralizing antibody. Therapeutic administration of epiregulin antibody reversed fibrosis in patient skin and lung explants, identifying it as a previously unexplored biologic drug target. Our findings reveal epiregulin as a crucial immune signal that maintains skin and lung fibrosis in multiple diseases and represents a promising antifibrotic target.
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