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http://hdl.handle.net/2445/172553
Title: | The transcription factor NFAT5 limits infection-induced type I interferon responses |
Author: | Huerga Encabo, Hector Traveset, Laia Argilaguet, Jordi Angulo Aguado, Ana Nistal Villán, Estanislao Jaiswal, Rahul Escalante, Carlos R. Gekas, Christos Meyerhans, Andreas Aramburu, Jose López Rodríguez, Cristina |
Keywords: | Interferó Macròfags Interferon Macrophages |
Issue Date: | 2020 |
Publisher: | Rockefeller University Press |
Abstract: | Type I interferon (IFN-I) provides effective antiviral immunity but can exacerbate harmful inflammatory reactions and cause hematopoietic stem cell (HSC) exhaustion; therefore, IFN-I expression must be tightly controlled. While signaling mechanisms that limit IFN-I induction and function have been extensively studied, less is known about transcriptional repressors acting directly on IFN-I regulatory regions. We show that NFAT5, an activator of macrophage pro-inflammatory responses, represses Toll-like receptor 3 and virus-induced expression of IFN-I in macrophages and dendritic cells. Mice lacking NFAT5 exhibit increased IFN-I production and better control of viral burden upon LCMV infection but show exacerbated HSC activation under systemic poly(I:C)-induced inflammation. We identify IFNβ as a primary target repressed by NFAT5, which opposes the master IFN-I inducer IRF3 by binding to an evolutionarily conserved sequence in the IFNB1 enhanceosome that overlaps a key IRF site. These findings illustrate how IFN-I responses are balanced by simultaneously opposing transcription factors. |
Note: | Reproducció del document publicat a: https://doi.org/10.1084/jem.20190449 |
It is part of: | Journal of Experimental Medicine, 2020, vol. 3, p. e20190449 |
URI: | http://hdl.handle.net/2445/172553 |
Related resource: | https://doi.org/10.1084/jem.20190449 |
ISSN: | 0022-1007 |
Appears in Collections: | Articles publicats en revistes (Biomedicina) |
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