| First Author | Huerga Encabo H | Year | 2020 |
| Journal | J Exp Med | Volume | 217 |
| Issue | 3 | PubMed ID | 31816635 |
| Mgi Jnum | J:289860 | Mgi Id | MGI:6432466 |
| Doi | 10.1084/jem.20190449 | Citation | Huerga Encabo H, et al. (2020) The transcription factor NFAT5 limits infection-induced type I interferon responses. J Exp Med 217(3) |
| abstractText | 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 IFNbeta 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. |
