CD177 on neutrophils engages stress-related behavioral changes in male mice

Persistent psychological stress can affect immune homeostasis and is a key factor in the development of depression. Many efforts are focused on the identifcation of pathways that link the immune system and mood disorders. Here, we found that psychological stress caused an increase in the frequency of brain-associated neutrophils and the level of neutrophil-specific antigen CD177 on peripheral neutrophils in male mice. Upregulated levels of blood CD177 are associated with depression in humans. Neutrophil depletion or Cd177 deficiency protected mice from stress-induced behavioral deficits. Importantly, adoptive transfer of CD177⁺ neutrophils from stressed mice increased the frequency of brain-associated leukocytes, including neutrophils, and caused behavioral defects in naive mice. These effects may be related to the endothelial adhesion advantage of CD177⁺ neutrophils and the interference of serine protease on endothelial junction. Our findings suggest a critical link between circulating CD177⁺ neutrophils and psychological stress-driven behavioral disorder.