Tonic interferon restricts pathogenic IL-17-driven inflammatory disease via balancing the microbiome
Maintenance of immune homeostasis involves a synergistic relationship between the host and the microbiome. Canonical interferon (IFN) signaling controls responses to acute microbial infection, through engagement of the STAT1 transcription factor. However, the contribution of tonic levels of IFN to i...
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eLife Sciences Publications Ltd
2021
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oai:doaj.org-article:982a4035ae764dbdbb7abc2f4d9fe2a72021-11-25T10:26:14ZTonic interferon restricts pathogenic IL-17-driven inflammatory disease via balancing the microbiome10.7554/eLife.683712050-084Xe68371https://doaj.org/article/982a4035ae764dbdbb7abc2f4d9fe2a72021-08-01T00:00:00Zhttps://elifesciences.org/articles/68371https://doaj.org/toc/2050-084XMaintenance of immune homeostasis involves a synergistic relationship between the host and the microbiome. Canonical interferon (IFN) signaling controls responses to acute microbial infection, through engagement of the STAT1 transcription factor. However, the contribution of tonic levels of IFN to immune homeostasis in the absence of acute infection remains largely unexplored. We report that STAT1 KO mice spontaneously developed an inflammatory disease marked by myeloid hyperplasia and splenic accumulation of hematopoietic stem cells. Moreover, these animals developed inflammatory bowel disease. Profiling gut bacteria revealed a profound dysbiosis in the absence of tonic IFN signaling, which triggered expansion of TH17 cells and loss of splenic Treg cells. Reduction of bacterial load by antibiotic treatment averted the TH17 bias and blocking IL17 signaling prevented myeloid expansion and splenic stem cell accumulation. Thus, tonic IFNs regulate gut microbial ecology, which is crucial for maintaining physiologic immune homeostasis and preventing inflammation.Isabelle J MariéLara BrambillaDoua AzzouzZe ChenGisele V BarachoAzlann ArnettHaiyan S LiWeiguo LiuLuisa CimminoPratip ChattopadhyayGregg SilvermanStephanie S WatowichBernard KhorDavid E LevyeLife Sciences Publications LtdarticleinterferoninflammationhomeostasisTh17hematopoietic stem cellsmicrobiomeMedicineRScienceQBiology (General)QH301-705.5ENeLife, Vol 10 (2021) |
| institution |
DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
interferon inflammation homeostasis Th17 hematopoietic stem cells microbiome Medicine R Science Q Biology (General) QH301-705.5 |
| spellingShingle |
interferon inflammation homeostasis Th17 hematopoietic stem cells microbiome Medicine R Science Q Biology (General) QH301-705.5 Isabelle J Marié Lara Brambilla Doua Azzouz Ze Chen Gisele V Baracho Azlann Arnett Haiyan S Li Weiguo Liu Luisa Cimmino Pratip Chattopadhyay Gregg Silverman Stephanie S Watowich Bernard Khor David E Levy Tonic interferon restricts pathogenic IL-17-driven inflammatory disease via balancing the microbiome |
| description |
Maintenance of immune homeostasis involves a synergistic relationship between the host and the microbiome. Canonical interferon (IFN) signaling controls responses to acute microbial infection, through engagement of the STAT1 transcription factor. However, the contribution of tonic levels of IFN to immune homeostasis in the absence of acute infection remains largely unexplored. We report that STAT1 KO mice spontaneously developed an inflammatory disease marked by myeloid hyperplasia and splenic accumulation of hematopoietic stem cells. Moreover, these animals developed inflammatory bowel disease. Profiling gut bacteria revealed a profound dysbiosis in the absence of tonic IFN signaling, which triggered expansion of TH17 cells and loss of splenic Treg cells. Reduction of bacterial load by antibiotic treatment averted the TH17 bias and blocking IL17 signaling prevented myeloid expansion and splenic stem cell accumulation. Thus, tonic IFNs regulate gut microbial ecology, which is crucial for maintaining physiologic immune homeostasis and preventing inflammation. |
| format |
article |
| author |
Isabelle J Marié Lara Brambilla Doua Azzouz Ze Chen Gisele V Baracho Azlann Arnett Haiyan S Li Weiguo Liu Luisa Cimmino Pratip Chattopadhyay Gregg Silverman Stephanie S Watowich Bernard Khor David E Levy |
| author_facet |
Isabelle J Marié Lara Brambilla Doua Azzouz Ze Chen Gisele V Baracho Azlann Arnett Haiyan S Li Weiguo Liu Luisa Cimmino Pratip Chattopadhyay Gregg Silverman Stephanie S Watowich Bernard Khor David E Levy |
| author_sort |
Isabelle J Marié |
| title |
Tonic interferon restricts pathogenic IL-17-driven inflammatory disease via balancing the microbiome |
| title_short |
Tonic interferon restricts pathogenic IL-17-driven inflammatory disease via balancing the microbiome |
| title_full |
Tonic interferon restricts pathogenic IL-17-driven inflammatory disease via balancing the microbiome |
| title_fullStr |
Tonic interferon restricts pathogenic IL-17-driven inflammatory disease via balancing the microbiome |
| title_full_unstemmed |
Tonic interferon restricts pathogenic IL-17-driven inflammatory disease via balancing the microbiome |
| title_sort |
tonic interferon restricts pathogenic il-17-driven inflammatory disease via balancing the microbiome |
| publisher |
eLife Sciences Publications Ltd |
| publishDate |
2021 |
| url |
https://doaj.org/article/982a4035ae764dbdbb7abc2f4d9fe2a7 |
| work_keys_str_mv |
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| _version_ |
1718413573572526080 |