Immunomodulatory aged neutrophils are augmented in blood and skin of psoriasis patients
Yessica Alina Rodriguez-Rosales, Jeroen D. Langereis, Mark A.J. Gorris, J.M.P.A. van den Reek, Esther Fasse, Mihai G. Netea, I. Jolanda M. de Vries, Laia Gómez-Muñoz, Bram van Cranenbroek, Andreas Körber, Wiebke Sondermann, Irma Joosten, E.M.G.J. de Jong, Hans J. P. M. Koenen
Abstract
BACKGROUND: Neutrophil accumulation in the skin is a hallmark of psoriasis. Novel insights on neutrophil phenotypic and functional heterogeneity raise the question to what extent these cells contribute to the sustained inflammatory skin reaction. OBJECTIVE: We sought to examine the phenotype and functional properties of neutrophils in blood and skin of patients with psoriasis, and the effect of TNF-α and p40(IL-12/IL-23) antibody therapy on circulating neutrophils. METHODS: Thirty-two patients with psoriasis were enrolled in an observational study performed in 2 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: neutrophils, different maturation stages were observed, including a subset resembling aged neutrophils that was 3 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 neutrophil extracellular trap 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. CONCLUSIONS: Patients with psoriasis reveal a unique neutrophil profile in circulation, and 2 distinct neutrophil subsets are present in psoriatic skin. Targeted biological treatment may aid in the containment of sustained neutrophil-mediated inflammation.