IFNß is a Novel Effector Cytokine in Resolving Inflammation

The engulfment of apoptotic leukocytes (efferocytosis) by macrophages during the resolution of inflammation is essential for tissue homeostasis and results in macrophage reprogramming/immune-silencing. However, a distinct subset of resolution phase macrophages loss their phagocytic capacity following intense efferocytosis, and hence were termed satiated macrophages. Here, we show using an unbiased RNA-Seq analysis that satiated macrophages express a distinct IFN-ß-related signature. Consequently, we determined IFN-ß is a bona fide pro-resolving cytokine that exerts various inflammation-terminating functions in vivo and ex vivo, such as enhancing PMN apoptosis and promoting macrophage efferocytosis as well as their reprogramming to pro-resolving phenotypes. Thus, IFN-ß is a novel multi-pronged effector cytokine in resolving inflammation.