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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.
Pubmed ID: 30824326
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Software for single-cell flow cytometry analysis. Its functions include management, display, manipulation, analysis and publication of the data stream produced by flow and mass cytometers.
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View all literature mentionsThis monoclonal targets MHC Class II (I-A/I-E)
View all literature mentionsgene symbol note: interleukin 17 receptor A mutant strain targeted mutation 1e, Wellcome Trust Sanger Institute This is a legacy resource.
View all literature mentionsMus musculus with name B6N.129S5-Il17btm1Lex/Mmucd from MMRRC.
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View all literature mentionsMus musculus with name B6;129S5-Il17rbtm1Lex/Mmucd from MMRRC.
View all literature mentionsMus musculus with name B6N.129S5-Il17retm1Lex/Mmucd from MMRRC.
View all literature mentionsMus musculus with name B6.129-Tlr2tm1Kir/J from IMSR.
View all literature mentionsMus musculus with name B6.129S2-Il6tm1Kopf/J from IMSR.
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