Top: Type III interferon alters the nuclear localization of the transcriptional co-regulator YAP during wound healing of human bronchial epithelial cells. Micrographs show localization or YAP (red) relative to the cell nucleus (blue) in cells adjacent to a scratch in the monolayer (dark area, right of images). In untreated cultures, YAP is present in most nuclei (purple nuclei, left panel) whereas in the presence of Type III interferon, the percentage of cells with nuclear YAP is greatly reduced (blue nuclei, right panel). Image credit: Krupakar Subramaniam. Bottom: Model. Type III and Type I IFN receptor signaling activate LATS1 to curtail tissue repair during acute viral infection. Left-hand panel: During acute viral infection, high concentrations of Type III and/or Type I IFN receptor signaling trigger JAK-dependent, STAT1-independent phosphorylation of LATS1, leading to phosphorylation and degradation of YAP and reduced tissue repair activities mediated by YAP target genes. In rapidly proliferating cell types, active LATS1/2 also blocks repair in part via a p53-dependent mechanism. Right-hand panel: During resolution of viral infection, lower concentrations of Type III and/or Type I IFN may continue to activate STAT1-mediated antiviral defenses but no longer activate LATS1/2, allowing epithelial repair to resume.
#Interferons protect against #ViralInfection, but can hinder tissue repair - how? @ellenfoxman.bsky.social &co show that high IFN levels suppress #BronchialCell migration & proliferation during tissue repair via JAK-driven LATS1 activation, independent of STAT1 @plosbiology.org 🧪 plos.io/4k1pyKA
