Aging neutrophils

Aged neutrophils are known to upregulate the chemokine receptor CXCR4, which might allow their clearance from the bone marrow, and downregulate L-selectin (CD62L). In Nature, Frenette and colleagues show that aged circulating CD62L^loCXCR4^hi neutrophils in mice have more activation of integrin α_Mβ₂ (Mac-1) and greater ROS production and form neutrophil extracellular traps. Aged neutrophils are distinct from activated neutrophils but upregulate several activation pathways, including adhesion pathways and signaling via TLRs, NLRs and NF-κB. Microbiota-derived signals induce neutrophil aging through TLR2-, TLR4- and MyD88-mediated pathways but not TNF- or GM-CSF-mediated pathways. Mouse models and patients with sickle cell disease have a greater number of aged neutrophils, and antibiotic treatment lowers the total number of neutrophils and the frequency of aged neutrophils in both mice and humans.

Nature 525, 528–532 (2015)