A genetically encoded reporter reveals interferon responses in multiple cell lineages

Interferons (IFNs) are canonical antiviral cytokines with emerging homeostatic functions across tissues, including in the brain. To date, a lack of tools to visualize IFN-responsive cells has limited our understanding of the breadth and nature of IFN signaling. Here we developed a novel and bright mouse reporter of IFN responses called IFN-brite, Bright Reporter of Interferon sTimulated gene Expression, consisting of two copies of the bright and fast-maturing green fluorescent fluorophore mGreenLantern downstream of the native <i>Isg15</i> gene. <i>Isg15</i> is one of the most abundant interferon stimulated genes (ISGs) and is detected in many cell types, including immune, stromal, and neuronal cells. Using in vivo and in vitro cytokine delivery, we show that IFN-brite is preferentially sensitive to IFN-β, with detectable but lower sensitivity responses to IFN-γ. We also detect IFN-brite signals in most brain cell types and in stromal and hematopoietic cells in the lung after influenza A infection. These data define a broadly useful new tool for studying IFN responses and suggest that diverse cell types, including neurons, can respond to IFNs.