1. Type I interferons link viral infection to enhanced epithelial turnover and repair.
- Author
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Sun L, Miyoshi H, Origanti S, Nice TJ, Barger AC, Manieri NA, Fogel LA, French AR, Piwnica-Worms D, Piwnica-Worms H, Virgin HW, Lenschow DJ, and Stappenbeck TS
- Subjects
- Animals, Epithelial Cells drug effects, Epithelium physiology, Female, GTP-Binding Proteins deficiency, Gene Expression Profiling, Male, Mice, Knockout, Molecular Sequence Data, Sequence Analysis, DNA, Signal Transduction, Epithelial Cells physiology, Epithelium immunology, Interferon Type I metabolism, Virus Diseases immunology
- Abstract
The host immune system functions constantly to maintain chronic commensal and pathogenic organisms in check. The consequences of these immune responses on host physiology are as yet unexplored, and may have long-term implications in health and disease. We show that chronic viral infection increases epithelial turnover in multiple tissues, and the antiviral cytokines type I interferons (IFNs) mediate this response. Using a murine model with persistently elevated type I IFNs in the absence of exogenous viral infection, the Irgm1(-/-) mouse, we demonstrate that type I IFNs act through nonepithelial cells, including macrophages, to promote increased epithelial turnover and wound repair. Downstream of type I IFN signaling, the highly related IFN-stimulated genes Apolipoprotein L9a and b activate epithelial proliferation through ERK activation. Our findings demonstrate that the host immune response to chronic viral infection has systemic effects on epithelial turnover through a myeloid-epithelial circuit., (Copyright © 2015 Elsevier Inc. All rights reserved.)
- Published
- 2015
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