Immunomodulatory aged neutrophils are augmented in blood and skin of psoriasis patients

Abstract Background Neutrophil accumulation in the skin is a hallmark of psoriasis. Novel insights on neutrophil phenotypic and functional heterogeneity raises the question to what extent these cells contribute to the sustained inflammatory skin reaction. Objective To examine the phenotype and functional properties of neutrophils in blood and skin of psoriasis patients, and the effect of TNF-α and p40(IL-12/IL-23) antibody therapy on circulating neutrophils. Methods Thirty-two psoriasis patients were enrolled in an observational study performed in two university hospitals. We evaluated neutrophil phenotype and function using in-vitro (co)culture stimulation assays, flow cytometry, multiplex immunohistochemistry and multispectral imaging of patient derived blood and skin samples. Results CD10pos and CD10neg neutrophils were increased in peripheral blood of psoriasis patients. In CD10neg neutrophils, different maturation stages were observed, including a subset resembling aged neutrophils that was three times more abundant than in healthy individuals. These aged neutrophils displayed suboptimal canonical neutrophil functions and induced IL-17 and IFN-γ production by T-cells in vitro, mediated by NET formation. Also, mature and aged neutrophils were present in psoriatic skin and were found in the vicinity of T-cells. Upon antibody therapy, numbers of these cells in circulation decreased. Conclusion Psoriatic patients reveal a unique neutrophil profile in circulation, and two distinct neutrophils subsets are present in psoriatic skin. Targeted biological treatment may aid in the containment of sustained neutrophil-mediated inflammation.