Yessica A Rodriguez-Rosales1, Jeroen D Langereis1, Mark A J Gorris2, Juul M P A van den Reek3, Esther Fasse1, Mihai G Netea4, I Jolanda M de Vries2, Laia Gomez-Muñoz1, Bram van Cranenbroek1, Andreas Körber5, Wiebke Sonderman5, Irma Joosten1, Elke M G J de Jong3, Hans J P M Koenen6. 1. Department of Laboratory Medicine, Laboratory of Medical Immunology, Radboudumc, Nijmegen, The Netherlands. 2. Department of Tumor Immunology, Radboudumc, Nijmegen, The Netherlands. 3. Department of Dermatology, Radboudumc, Nijmegen, The Netherlands. 4. Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboudumc, Nijmegen, The Netherlands; Department for Genomics & Immunoregulation, Life and Medical Sciences Institute (LIMES), University of Bonn, Bonn, Germany. 5. Department of Dermatology, University Hospital of Essen, Essen, Germany. 6. Department of Laboratory Medicine, Laboratory of Medical Immunology, Radboudumc, Nijmegen, The Netherlands. Electronic address: Hans.Koenen@radboudumc.nl.
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: 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. 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.
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: 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. 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.
Authors: Marija V Medovic; Vladimir Lj Jakovljevic; Vladimir I Zivkovic; Nevena S Jeremic; Jovana N Jeremic; Sergey B Bolevich; Ana B Ravic Nikolic; Vesna M Milicic; Ivan M Srejovic Journal: Oxid Med Cell Longev Date: 2022-03-12 Impact factor: 6.543