Dysregulated Lung Commensal Bacteria Drive Interleukin-17B Production to Promote Pulmonary Fibrosis through Their Outer Membrane Vesicles
Open accessAbstract
Idiopathic pulmonary fibrosis (IPF) is a severe form of lung fibrosis with a high mortality rate. However, the etiology of IPF remains unknown. Here, we report that alterations in lung microbiota critically promote pulmonary fibrosis pathogenesis. We found that lung microbiota was dysregulated, and the dysregulated microbiota in turn induced production of interleukin-17B (IL-17B) during bleomycin-induced mouse lung fibrosis. Either lung-microbiota depletion or IL-17B deficiency ameliorated the disease progression. IL-17B cooperated with tumor necrosis factor-α to induce expression of neutrophil-recruiting genes and T helper 17 (Th17)-cell-promoting genes. Three pulmonary commensal microbes, which belong to the genera Bacteroides and Prevotella, were identified to promote fibrotic pathogenesis through IL-17R signaling. We further defined that the outer membrane vesicles (OMVs) that were derived from the identified commensal microbes induced IL-17B production through Toll-like receptor-Myd88 adaptor signaling. Together our data demonstrate that specific pulmonary symbiotic commensals can promote lung fibrosis by regulating a profibrotic inflammatory cytokine network.
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IL-13 may promote fibrosis independently of TGF-β, in part by directly targeting stromal and parenchymal cells, including epithelial populations and collagen-producing myofibroblasts.
“it may promote fibrosis independently of TGF-β134 in part by directly targeting stromal and parenchymal cells, including epithelial populations and collagen-producing myofibroblasts135”
From Fibrosis: from mechanisms to medicines (2020) · cites this paper as [135]
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- Authors
- Yang, D., Chen, X., Wang, J., Lou, Q., Lou, Y., Li, L., Wang, H., Chen, J., Wu, M., Song, X., & Qian, Y.
- Affiliations
- Shanghai Institute of Nutrition and Health (CN)
- Shanghai Jiao Tong University (CN)
- Shanghai University of Traditional Chinese Medicine (CN)
- Chinese Academy of Sciences (CN)
- Harvard University (US)
- ShanghaiTech University (CN)
- Corresponding author
- Qian, Youcun
- ORCID
- Venue
- Immunity
- Publisher
- Elsevier BV
- Published
- 2019-03
- Volume
- 50
- Issue
- 3
- Pages
- 692-706.e7
- ISSN
- 1074-7613 (ISSN-L)
- OpenAlex
- W2916308866
- Cited by
- 250
- References
- 46
- Citations by year
- 2026: 20 · 2025: 42 · 2024: 50 · 2023: 34 · 2022: 45 · 2021: 19 · 2020: 31 · 2019: 9
- FWCI
- 19.09
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Immunity (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (91842306, 81430036, 81830018, 91429307, 91542119, 31500707)
- National Key R&D Program of China (2018YFA0507402)
- Strategic Priority Research Program of the Chinese Academy of Sciences (XDB19000000)
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Life Sciences › Immunology and Microbiology › Microbiology › Microbial infections and disease research
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Occupational and environmental lung diseases
- Keywords
- idiopathic pulmonary fibrosis, lung microbiome, commensal bacteria, outer membrane vesicles, Bacteroides, Prevotella, Th17 cells, neutrophil recruitment, TLR4, MyD88, bleomycin-induced lung fibrosis, TNF-α
- MeSH terms
- Animals, Bacterial Outer Membrane Proteins, Bacteroides, Disease Models, Animal, Inflammation, Lung, Mice, Inbred C57BL, Neutrophils, Tumor Necrosis Factor-alpha, Signal Transduction, Cytokines, Prevotella, Interleukin-17, Toll-Like Receptors, Mice, Myeloid Differentiation Factor 88, Idiopathic Pulmonary Fibrosis, Microbiota
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