# name
The transcription factor NFAT5 limits infection-induced type I interferon responses

# metadata.dc.description.abstract[].value
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.

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Journal of Experimental Medicine, 2020, vol. 3, p. e20190449

# metadata.dc.rights[].value
cc by-nc-sa (c)  Huerga Encabo et al., 2020

# metadata.dc.source[].value
Articles publicats en revistes (Biomedicina)

# metadata.dc.title[].value
The transcription factor NFAT5 limits infection-induced type I interferon responses