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Publication : Tonic interferon restricts pathogenic IL-17-driven inflammatory disease via balancing the microbiome.

First Author  Marié IJ Year  2021
Journal  Elife Volume  10
PubMed ID  34378531 Mgi Jnum  J:316929
Mgi Id  MGI:6765776 Doi  10.7554/eLife.68371
Citation  Marie IJ, et al. (2021) Tonic interferon restricts pathogenic IL-17-driven inflammatory disease via balancing the microbiome. Elife 10:e68371
abstractText  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.
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