Neutrophils are the most abundant cells of the immune system, and their population therefore requires careful regulation. Bensinger and colleagues in the Journal of Clinical Investigation identify a pivotal action of the liver X receptors (LXRs) in neutrophil homeostasis. Knocking out LXRα and LXRβ leads to many more neutrophils but has no apparent intrinsic effect on the neutrophils themselves. Senescent neutrophils are normally cleared by macrophages, which elicits a negative feedback signal against granulopoiesis. Accordingly, the authors find that engulfment of apoptotic neutrophils by macrophages activates LXR signaling, which then downregulates their expression of interleukin 23 (IL-23). This decrease in IL-23 in turn diminishes the abundance of IL-17+ cells in the spleen and, critically, the amount of the granulopoietic cytokine G-CSF. Phagocyte LXRs therefore are important both in mediating the tolerogenic signals to phagocytes and in the process of neutrophil homeostasis.

J. Clin. Invest. (12 January 2012) doi:10.1172/JCI58393