ArticleAmerican journal of physiology. Lung cellular and molecular physiology2017
Repetitive intradermal bleomycin injections evoke T-helper cell 2 cytokine-driven pulmonary fibrosis.
Article in American journal of physiology. Lung cellular and molecular physiology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 43 citations in OpenAlex.
- Collaborative functionality between three types of inflammation in idiopathic pulmonary fibrosis.Nature immunology · 2026Review
- Vitronectin metabolically programs profibrotic macrophages in 3D cultures and idiopathic pulmonary fibrosis.Science advances · 2026Article
- Unleashing innovative cross-organ fibrosis therapies by harnessing the omics revolution.JCI insight · 2026Review
- The DDR1 Tyrosine Kinase Promotes Th17 Cell Migration in Three-Dimensional Collagen and into the Joints During Inflammatory Arthritis.International journal of molecular sciences · 2026Article
- The role of immune cell crosstalk and signaling pathways in the pathogenesis of pulmonary fibrosis.Molecular biology reports · 2026Review
- Advances in understanding the role of interleukins in pulmonary fibrosis (Review).Experimental and therapeutic medicine · 2025Review
- Hedgehog Signaling Pathway in Fibrosis and Targeted Therapies.Biomolecules · 2024Review
- Review
- SEMA3B inhibits TGFβ-induced extracellular matrix protein production and its reduced levels are associated with a decline in lung function in IPF.American journal of physiology. Cell physiology · 2024Article
- Searching for an Animal Model with Clinical Features of Scleroderma.American journal of respiratory cell and molecular biology · 2023Article
- Pulmonary inflammation and fibroblast immunoregulation: from bench to bedside.The Journal of clinical investigation · 2023Review
- Interleukin-13 contributes to the occurrence of oral submucosal fibrosis.Journal of cellular and molecular medicine · 2023Article
- Article
- Conventional and pathogenic Th2 cells in inflammation, tissue repair, and fibrosis.Frontiers in immunology · 2022Review
- The interplay of DAMPs, TLR4, and proinflammatory cytokines in pulmonary fibrosis.Journal of molecular medicine (Berlin, Germany) · 2021Review
- Extracellular CIRP Induces an Inflammatory Phenotype in Pulmonary FibroblastsFrontiers in immunology · 2021Article
- The Protective Effects of IL-31RA Deficiency During Bleomycin-Induced Pulmonary Fibrosis.Frontiers in immunology · 2021Article
- Fibrosis: from mechanisms to medicines.Nature · 2020Review
- Inhibition of Aurora Kinase B attenuates fibroblast activation and pulmonary fibrosis.EMBO molecular medicine · 2020Article
- Fibrocyte accumulation in the lungs of cystic fibrosis patients.Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society · 2020Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
Abstract
IL-4 and IL-13 are major T-helper cell (Th) 2 cytokines implicated in the pathogenesis of several lung diseases, including pulmonary fibrosis. In this study, using a novel repetitive intradermal bleomycin model in which mice develop extensive lung fibrosis and a progressive decline in lung function compared with saline-treated control mice, we investigated profibrotic functions of Th2 cytokines. To determine the role of IL-13 signaling in the pathogenesis of bleomycin-induced pulmonary fibrosis, wild-type, IL-13, and IL-4Rα-deficient mice were treated with bleomycin, and lungs were assessed for changes in lung function and pulmonary fibrosis. Histological staining and lung function measurements demonstrated that collagen deposition and lung function decline were attenuated in mice deficient in either IL-13 or IL-4Rα-driven signaling compared with wild-type mice treated with bleomycin. Furthermore, our results demonstrated that IL-13 and IL-4Rα-driven signaling are involved in excessive migration of macrophages and fibroblasts. Notably, our findings demonstrated that IL-13-driven migration involves increased phospho-focal adhesion kinase signaling and F-actin polymerization. Importantly, in vivo findings demonstrated that IL-13 augments matrix metalloproteinase (MMP)-2 and MMP9 activity that has also been shown to increase migration and invasiveness of fibroblasts in the lungs during bleomycin-induced pulmonary fibrosis. Together, our findings demonstrate a pathogenic role for Th2-cytokine signaling that includes excessive migration and protease activity involved in severe fibrotic lung disease.
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Registered trials
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