Type I interferons link viral infection to enhanced epithelial turnover and repair.

Type I interferons link viral infection to enhanced epithelial turnover and repair.
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DOI:
10.1016/j.chom.2014.11.004
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发表时间:
2015-01-14
影响因子:
30.3
通讯作者:
Stappenbeck TS
Stappenbeck TS
中科院分区:
医学1区
文献类型:
--
作者:
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;Stappenbeck TS

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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 increased epithelial turnover in multiple tissues, and the antiviral cytokines Type I interferons (IFNs) mediates 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 non-epithelial 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.
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