STAT3 operates as an inflammation-dependent transcriptional switch in antiviral NK cells.

STAT3 acts as a cytokine-sensing transcriptional switch in antiviral NK cells during MCMV infection, promoting or impairing adaptive NK cell responses depending on whether IL-15 or type I interferon dominates the inflammatory milieu. Recruited to distinct genomic loci under each cytokine, STAT3 drives alternative transcriptional programs by differentially regulating MYB and BLIMP-1, with relocation governed by epigenetic mechanisms and STAT motif preference. The work reframes a canonical cytokine effector as a context-dependent integrator of inflammatory signals in lymphocyte adaptation.