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

• Published in: Journal of allergy and clinical immunology 2021-10, Vol.148 (4), p.1030-1040
• Main Authors: Rodriguez-Rosales, Yessica A., Langereis, Jeroen D., Gorris, Mark A.J., van den Reek, Juul M.P.A., Fasse, Esther, Netea, Mihai G., de Vries, I. Jolanda M., Gomez-Muñoz, Laia, van Cranenbroek, Bram, Körber, Andreas, Sondermann, Wiebke, Joosten, Irma, de Jong, Elke M.G.J., Koenen, Hans J.P.M.
• Format: Article
• Language: English
• Subjects: aged neutrophils; antibody therapy; IL-17; inflammatory disease; netosis; neutrophil extracellular traps; Neutrophil heterogeneity; neutrophil maturation; neutrophils in psoriatic skin; psoriasis
• ISSN: 0091-6749; 1097-6825
• DOI: 10.1016/j.jaci.2021.02.041

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. 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. 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. Cluster of differentiation (CD)10pos and CD10neg neutrophils were increased in peripheral blood of patients with psoriasis. In CD10neg 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. 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. [Display omitted]