Dysregulated Lung Commensal Bacteria Drive Interleukin-17B Production to Promote Pulmonary Fibrosis through Their Outer Membrane Vesicles
Dysregulated Lung Commensal Bacteria Drive Interleukin-17B Production to Promote Pulmonary Fibrosis through Their Outer Membrane Vesicles
复制标题
失调的肺共生细菌通过外膜囊泡驱动白细胞介素 17B 的产生，从而促进肺纤维化
DOI：
10.1016/j.immuni.2019.02.001
复制
发表时间：
2019-03-19
期刊：
影响因子：
32.4
通讯作者：
Qian, Youcun
中科院分区：
文献类型：
--
作者：
Yang, Daping;Chen, Xi;Qian, Youcun
特发性肺纤维化(IPF)是一种严重的肺纤维化，病死率高。然而，IPF的病因仍不清楚。在此，我们报告了肺微生物区系的改变对肺纤维化发病机制的重要促进作用。我们发现，在博莱霉素诱导的小鼠肺纤维化过程中，肺微生物区系失调，而这种失调的微生物区系又诱导了白介素17B(IL-17B)的产生。肺微生物区系耗竭或IL-17B缺乏均可缓解疾病进展。IL-17B与肿瘤坏死因子-a协同诱导中性粒细胞募集基因和辅助性T细胞17(Th17)细胞促进基因的表达。通过IL-17R信号转导途径，鉴定了拟杆菌属和普氏杆菌属的三种肺内共生微生物促进肺纤维化的发生。我们进一步确定，来自已鉴定的共生微生物的外膜小泡(OMV)通过Toll样受体-MyD88接头信号诱导IL-17B的产生。总之，我们的数据表明，特定的肺共生可以通过调节促纤维化的炎性细胞因子网络来促进肺纤维化。
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-a 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.