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Understanding the control of type I interferon responses during infection

05.06.2021

 

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

 

Huerga Encabo, H., Traveset, L., Argilaguet, J., Angulo, A., Nistal-Villán, E., Jaiswal, R., Escalante, C.R., Gekas, C., Meyerhans, A., Aramburu, J. and López-Rodríguez, C. (2020) The transcription factor NFAT5 limits infection-induced type I interferon responses. J. Exp. Med. 217 (3): e20190449.

 

Type I interferon (IFN-I) provides antiviral immunity, but also exacerbates autoimmune diseases and hematopoietic stem cell (HSC) exhaustion. While multiple mechanisms inducing IFN-I responses have been identified, much less is known about IFN-I repressive mechanisms operating at the transcription level. Here we show that NFAT5, an inducer of inflammatory responses, can repress IFN-I transcription by competing against IRF3, a key IFN-I-inducing factor, at the IFNB1 enhanceosome. NFAT5-deficient cells show enhanced IFN-I responses to viral infection in vitro and in vivo, and NFAT5-deficient mice display better control of the viral load upon infection. However, elevated IFN-I in these mice can lead to HSC overactivation, which if persisting can weaken blood regeneration capacity. Our work reveals how IFN-I responses are controlled by an evolutionarily conserved mechanism that relies on the balance between simultaneously opposing regulators. 

 

Understanding the control of type I interferon responses during infection.

 

 

 

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