Marie T. Moog, Melina Baltes, Tina Röpke, Franziska Aschenbrenner, Regina Maus, Jennifer Stolper, Danny Jonigk, Immo Prinz, Martin Kolb, Ulrich A. Maus
{"title":"先天性 T 细胞衍生的 IL-17A/F 可保护小鼠免受博莱霉素诱导的急性肺损伤,但不能保护小鼠免受博莱霉素或腺病毒 TGF-β1 诱导的肺纤维化。","authors":"Marie T. Moog, Melina Baltes, Tina Röpke, Franziska Aschenbrenner, Regina Maus, Jennifer Stolper, Danny Jonigk, Immo Prinz, Martin Kolb, Ulrich A. Maus","doi":"10.1002/eji.202451323","DOIUrl":null,"url":null,"abstract":"<p>The pathobiology of IL-17 in lung fibrogenesis is controversial. Here we examined the role of IL-17A/F in bleomycin (BLM) and adenoviral TGF-β1-induced lung fibrosis in mice. In both experimental models, WT and <i>IL17af<sup>−/−</sup></i> mice showed increased collagen contents and remodeled lung architecture as assessed by histopathological examination, suggesting that IL-17A/F is dispensable for lung fibrogenesis. However, <i>IL17af<sup>−/−</sup></i> mice responded to the BLM challenge with perturbed lung leukocyte subset recruitment. More specifically, bleomycin triggered angiocentric neutrophilic infiltrations of the lung accompanied by increased mortality of <i>IL17af</i><sup>−/−</sup> but not WT mice. WT bone marrow transplantation failed to correct this phenotype in BLM-challenged <i>IL17af</i><sup>−/−</sup> mice. Conversely, <i>IL17a/f</i><sup>−/−</sup> bone marrow transplantation → WT did not perturb lung leukocytic responses upon BLM. At the same time, <i>IL17af<sup>−/−</sup></i> mice treated with recombinant IL-17A/F showed an attenuated lung inflammatory response to BLM. Together, the data show that the degree of BLM-driven acute lung injury was critically dependent on the presence of IL-17A/F, while in both models, the fibrotic remodeling process was not.</p>","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":"54 12","pages":""},"PeriodicalIF":4.5000,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11628887/pdf/","citationCount":"0","resultStr":"{\"title\":\"Innate T-cell-derived IL-17A/F protects from bleomycin-induced acute lung injury but not bleomycin or adenoviral TGF-β1-induced lung fibrosis in mice\",\"authors\":\"Marie T. Moog, Melina Baltes, Tina Röpke, Franziska Aschenbrenner, Regina Maus, Jennifer Stolper, Danny Jonigk, Immo Prinz, Martin Kolb, Ulrich A. Maus\",\"doi\":\"10.1002/eji.202451323\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p>The pathobiology of IL-17 in lung fibrogenesis is controversial. Here we examined the role of IL-17A/F in bleomycin (BLM) and adenoviral TGF-β1-induced lung fibrosis in mice. In both experimental models, WT and <i>IL17af<sup>−/−</sup></i> mice showed increased collagen contents and remodeled lung architecture as assessed by histopathological examination, suggesting that IL-17A/F is dispensable for lung fibrogenesis. However, <i>IL17af<sup>−/−</sup></i> mice responded to the BLM challenge with perturbed lung leukocyte subset recruitment. More specifically, bleomycin triggered angiocentric neutrophilic infiltrations of the lung accompanied by increased mortality of <i>IL17af</i><sup>−/−</sup> but not WT mice. WT bone marrow transplantation failed to correct this phenotype in BLM-challenged <i>IL17af</i><sup>−/−</sup> mice. Conversely, <i>IL17a/f</i><sup>−/−</sup> bone marrow transplantation → WT did not perturb lung leukocytic responses upon BLM. At the same time, <i>IL17af<sup>−/−</sup></i> mice treated with recombinant IL-17A/F showed an attenuated lung inflammatory response to BLM. Together, the data show that the degree of BLM-driven acute lung injury was critically dependent on the presence of IL-17A/F, while in both models, the fibrotic remodeling process was not.</p>\",\"PeriodicalId\":165,\"journal\":{\"name\":\"European Journal of Immunology\",\"volume\":\"54 12\",\"pages\":\"\"},\"PeriodicalIF\":4.5000,\"publicationDate\":\"2024-09-05\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11628887/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"European Journal of Immunology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://onlinelibrary.wiley.com/doi/10.1002/eji.202451323\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"IMMUNOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"European Journal of Immunology","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1002/eji.202451323","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
Innate T-cell-derived IL-17A/F protects from bleomycin-induced acute lung injury but not bleomycin or adenoviral TGF-β1-induced lung fibrosis in mice
The pathobiology of IL-17 in lung fibrogenesis is controversial. Here we examined the role of IL-17A/F in bleomycin (BLM) and adenoviral TGF-β1-induced lung fibrosis in mice. In both experimental models, WT and IL17af−/− mice showed increased collagen contents and remodeled lung architecture as assessed by histopathological examination, suggesting that IL-17A/F is dispensable for lung fibrogenesis. However, IL17af−/− mice responded to the BLM challenge with perturbed lung leukocyte subset recruitment. More specifically, bleomycin triggered angiocentric neutrophilic infiltrations of the lung accompanied by increased mortality of IL17af−/− but not WT mice. WT bone marrow transplantation failed to correct this phenotype in BLM-challenged IL17af−/− mice. Conversely, IL17a/f−/− bone marrow transplantation → WT did not perturb lung leukocytic responses upon BLM. At the same time, IL17af−/− mice treated with recombinant IL-17A/F showed an attenuated lung inflammatory response to BLM. Together, the data show that the degree of BLM-driven acute lung injury was critically dependent on the presence of IL-17A/F, while in both models, the fibrotic remodeling process was not.
期刊介绍:
The European Journal of Immunology (EJI) is an official journal of EFIS. Established in 1971, EJI continues to serve the needs of the global immunology community covering basic, translational and clinical research, ranging from adaptive and innate immunity through to vaccines and immunotherapy, cancer, autoimmunity, allergy and more. Mechanistic insights and thought-provoking immunological findings are of interest, as are studies using the latest omics technologies. We offer fast track review for competitive situations, including recently scooped papers, format free submission, transparent and fair peer review and more as detailed in our policies.