Abstract
Draining lymph node neutrophils regulate inflammation
Neutrophil recruitment to the draining lymph node is a crucial step in various skin-related immune responses; however, the mechanism by which this occurs is unclear. Here, Özcan et al. used various skin inflammation and infection models to track the movement of neutrophils homing to and leaving the skin. They found that the skin neutrophils migrated to the skin-draining lymph nodes in a CCR7-mediated manner. In the draining lymph node, neutrophils were cleared by phagocytosis by conventional dendritic cells. These CCR7-driven neutrophils were crucial for protection against bacterial infection and TLR7 ligand–induced inflammation. Together, the migration of neutrophils from the skin to the draining lymph node, and their subsequent clearance, is important for skin immune responses.
Neutrophils are the first nonresident effector immune cells that migrate to a site of infection or inflammation; however, improper control of neutrophil responses can cause considerable tissue damage. Here, we found that neutrophil responses in inflamed or infected skin were regulated by CCR7-dependent migration and phagocytosis of neutrophils in draining lymph nodes (dLNs). In mouse models of Toll-like receptor–induced skin inflammation and cutaneous Staphylococcus aureus infection, neutrophils migrated from the skin to the dLNs via lymphatic vessels in a CCR7-mediated manner. In the dLNs, these neutrophils were phagocytosed by lymph node–resident type 1 and type 2 conventional dendritic cells. CCR7 up-regulation on neutrophils was a conserved mechanism across different tissues and was induced by a broad range of microbial stimuli. In the context of cutaneous immune responses, disruption of CCR7 interactions by selective CCR7 deficiency of neutrophils resulted in increased antistaphylococcal immunity and aggravated skin inflammation. Thus, neutrophil homing to and clearance in skin-dLNs affects cutaneous immunity versus pathology.
Özcan, A