Mus musculus strain:C57BL/6 Raw sequence reads. Mus musculus strain:C57BL/6

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 potential, and hence were termed satiated macrophages. Here, we show using an unbiased RNA-Seq analysis that satiated macrophages express a distinct IFNb-related signature. Unexpectedly, we found peritoneal IFNb levels peaked during the onset as well as the resolution phase of peritonitis. Consequently, we used IFNb-/- mice and neutralizing antibodies to determine IFNb limited the onset of neutrophilic inflammation by reducing peritoneal neutrophil numbers and enhancing their apoptosis. Moreover, IFNb enhanced macrophage efferocytosis and reprogramming to an anti-inflammatory phenotype. These findings indicate for the first time that IFNb is a key effector cytokine in resolving inflammation.