Authors:	Schaller, Theresa Ringen, Julia Fischer, Berenice Bieler, Tabea Perius, Katharina Knopp, Tanja Kommoss, Katharina S. Korn, Thomas Heikenwälder, Mathias Oelze, Matthias Daiber, Andreas Münzel, Thomas Kramer, Daniela Wenzel, Philip Wild, Johannes Karbach, Susanne Waisman, Ari
Title:	Reactive oxygen species produced by myeloid cells in psoriasis as a potential biofactor contributing to the development of vascular inflammation
Online publication date:	3-Aug-2023
Year of first publication:	2023
Language:	english
Abstract:	Psoriasis is an immune-mediated inflammatory skin disease driven by interleukin-17A (IL-17A) and associated with cardiovascular dysfunction. We used a severe psoriasis mouse model of keratinocyte IL-17A overexpression (K14-IL-17Aind/+, IL-17Aind/+ control mice) to investigate the activity of neutrophils and a potential cellular interconnection between skin and vasculature. Levels of dermal reactive oxygen species (ROS) and their release by neutrophils were measured by lucigenin-/luminol-based assays, respectively. Quantitative RT-PCR determined neutrophilic activity and inflammation-related markers in skin and aorta. To track skin-derived immune cells, we used PhAM-K14-IL-17Aind/+ mice allowing us to mark all cells in the skin by photoconversion of a fluorescent protein to analyze their migration into spleen, aorta, and lymph nodes by flow cytometry. Compared to controls, K14-IL-17Aind/+ mice exhibited elevated ROS levels in the skin and a higher neutrophilic oxidative burst accompanied by the upregulation of several activation markers. In line with these results psoriatic mice displayed elevated expression of genes involved in neutrophil migration (e.g., Cxcl2 and S100a9) in skin and aorta. However, no direct immune cell migration from the psoriatic skin into the aortic vessel wall was observed. Neutrophils of psoriatic mice showed an activated phenotype, but no direct cellular migration from the skin to the vasculature was observed. This suggests that highly active vasculature-invading neutrophils must originate directly from the bone marrow. Hence, the skin-vasculature crosstalk in psoriasis is most likely based on the systemic effects of the autoimmune skin disease, emphasizing the importance of a systemic therapeutic approach for psoriasis patients.
DDC:	610 Medizin 610 Medical sciences
Institution:	Johannes Gutenberg-Universität Mainz
Department:	FB 04 Medizin
Place:	Mainz
ROR:	https://ror.org/023b0x485
DOI:	http://doi.org/10.25358/openscience-9305
Version:	Published version
Publication type:	Zeitschriftenaufsatz
License:	CC BY-NC-ND
Information on rights of use:	https://creativecommons.org/licenses/by-nc-nd/4.0/
Journal:	Biofactors Version of Record (VoR)
Publisher:	Wiley
Publisher place:	Malden, Mass.
Issue date:	2023
ISSN:	1872-8081
Publisher DOI:	10.1002/biof.1949
Appears in collections:	DFG-491381577-H