Seung Hyeon Kim, Zachary White, Anastasiia Gainullina, Soeun Kang, Jiseon Kim, Joseph R. Dominguez, Yeonwoo Choi, Ivan Cabrera, Madison Plaster, Michihiro Takahama, Rafael S. Czepielewski, Jinki Yeom, Matthias Gunzer, Nissim Hay, Odile David, Nicolas Chevrier, Teruyuki Sano, Ki-Wook Kim
{"title":"肺间质巨噬细胞对IL-10的感知可防止细菌生态失调引起的肺部炎症并维持免疫稳态","authors":"Seung Hyeon Kim, Zachary White, Anastasiia Gainullina, Soeun Kang, Jiseon Kim, Joseph R. Dominguez, Yeonwoo Choi, Ivan Cabrera, Madison Plaster, Michihiro Takahama, Rafael S. Czepielewski, Jinki Yeom, Matthias Gunzer, Nissim Hay, Odile David, Nicolas Chevrier, Teruyuki Sano, Ki-Wook Kim","doi":"10.1016/j.immuni.2025.04.004","DOIUrl":null,"url":null,"abstract":"Crosstalk between the immune system and the microbiome is critical for maintaining immune homeostasis. Here, we examined this communication and the impact of immune-suppressive IL-10 signaling on pulmonary homeostasis. We found that IL-10 sensing by interstitial macrophages (IMs) is required to prevent spontaneous lung inflammation. Loss of IL-10 signaling in IMs initiated an inflammatory cascade through the activation of classical monocytes and CD4<sup>+</sup> T cell subsets, leading to chronic lung inflammation with age. Analyses of antibiotic-treated and germ-free mice established that lung inflammation in the animals lacking IL-10 signaling was triggered by commensal bacteria. 16S rRNA sequencing revealed <em>Delftia acidovorans</em> and <em>Rhodococcus erythropolis</em> as potential drivers of lung inflammation. Intranasal administration of these bacteria or transplantation of human fecal microbiota elicited lung inflammation in gnotobiotic <em>Il10</em>-deficient mice. These findings highlight that IL-10 sensing by IMs contributes to pulmonary homeostasis by preventing lung inflammation caused by commensal dysbiosis.","PeriodicalId":13269,"journal":{"name":"Immunity","volume":"137 1","pages":""},"PeriodicalIF":25.5000,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"IL-10 sensing by lung interstitial macrophages prevents bacterial dysbiosis-driven pulmonary inflammation and maintains immune homeostasis\",\"authors\":\"Seung Hyeon Kim, Zachary White, Anastasiia Gainullina, Soeun Kang, Jiseon Kim, Joseph R. Dominguez, Yeonwoo Choi, Ivan Cabrera, Madison Plaster, Michihiro Takahama, Rafael S. Czepielewski, Jinki Yeom, Matthias Gunzer, Nissim Hay, Odile David, Nicolas Chevrier, Teruyuki Sano, Ki-Wook Kim\",\"doi\":\"10.1016/j.immuni.2025.04.004\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"Crosstalk between the immune system and the microbiome is critical for maintaining immune homeostasis. Here, we examined this communication and the impact of immune-suppressive IL-10 signaling on pulmonary homeostasis. We found that IL-10 sensing by interstitial macrophages (IMs) is required to prevent spontaneous lung inflammation. Loss of IL-10 signaling in IMs initiated an inflammatory cascade through the activation of classical monocytes and CD4<sup>+</sup> T cell subsets, leading to chronic lung inflammation with age. Analyses of antibiotic-treated and germ-free mice established that lung inflammation in the animals lacking IL-10 signaling was triggered by commensal bacteria. 16S rRNA sequencing revealed <em>Delftia acidovorans</em> and <em>Rhodococcus erythropolis</em> as potential drivers of lung inflammation. Intranasal administration of these bacteria or transplantation of human fecal microbiota elicited lung inflammation in gnotobiotic <em>Il10</em>-deficient mice. These findings highlight that IL-10 sensing by IMs contributes to pulmonary homeostasis by preventing lung inflammation caused by commensal dysbiosis.\",\"PeriodicalId\":13269,\"journal\":{\"name\":\"Immunity\",\"volume\":\"137 1\",\"pages\":\"\"},\"PeriodicalIF\":25.5000,\"publicationDate\":\"2025-04-29\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Immunity\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1016/j.immuni.2025.04.004\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"IMMUNOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Immunity","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.immuni.2025.04.004","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
IL-10 sensing by lung interstitial macrophages prevents bacterial dysbiosis-driven pulmonary inflammation and maintains immune homeostasis
Crosstalk between the immune system and the microbiome is critical for maintaining immune homeostasis. Here, we examined this communication and the impact of immune-suppressive IL-10 signaling on pulmonary homeostasis. We found that IL-10 sensing by interstitial macrophages (IMs) is required to prevent spontaneous lung inflammation. Loss of IL-10 signaling in IMs initiated an inflammatory cascade through the activation of classical monocytes and CD4+ T cell subsets, leading to chronic lung inflammation with age. Analyses of antibiotic-treated and germ-free mice established that lung inflammation in the animals lacking IL-10 signaling was triggered by commensal bacteria. 16S rRNA sequencing revealed Delftia acidovorans and Rhodococcus erythropolis as potential drivers of lung inflammation. Intranasal administration of these bacteria or transplantation of human fecal microbiota elicited lung inflammation in gnotobiotic Il10-deficient mice. These findings highlight that IL-10 sensing by IMs contributes to pulmonary homeostasis by preventing lung inflammation caused by commensal dysbiosis.
期刊介绍:
Immunity is a publication that focuses on publishing significant advancements in research related to immunology. We encourage the submission of studies that offer groundbreaking immunological discoveries, whether at the molecular, cellular, or whole organism level. Topics of interest encompass a wide range, such as cancer, infectious diseases, neuroimmunology, autoimmune diseases, allergies, mucosal immunity, metabolic diseases, and homeostasis.