Low-density neutrophils preferentially infiltrate the skin compared to conventional neutrophils in an experimental...

Neutrophils infiltrate lesional skin robustly in individuals with psoriasis. However, their role in chronically inflamed skin-particularly in terms of phenotypic and functional diversity-remains poorly understood. In this study, we investigated the functional potential of 2 distinct circulating neutrophil populations-conventional, polymorphonuclear neutrophils (cNeu) and low-density neutrophils (LDNeu)-to infiltrate lesional skin in an experimental model of psoriasis. We found that, similar to human psoriasis, imiquimod-induced psoriasis-like dermatitis in mice is associated with elevated levels of circulating LDNeu. In this model, both cNeu and LDNeu partially recapitulate the phenotypes and in vitro chemotactic responses previously observed in neutrophils from psoriasis patients. These features include an increased tendency of LDNeu to interact with platelets and elevated expression of the chemokine receptor CXCR4, the latter of which is associated with a heightened proinflammatory phenotype. Using adoptive transfer of murine cNeu and LDNeu, we demonstrate that LDNeu preferentially accumulate in psoriasis-affected skin but not in normal skin. These findings highlight distinct intrinsic functional properties of neutrophil subsets, as reflected in their differential infiltration of chronically inflamed tissue. This work offers a plausible explanation for neutrophil heterogeneity in the skin and provides new insights into the pathophysiology of psoriasis.