Bridgewood, C, Fearnley, GW, Berekmeri, A et al. (6 more authors) (2018) IL-36 gamma Is a Strong Inducer of IL-23 in Psoriatic Cells and Activates Angiogenesis. Frontiers in Immunology, 9. ARTN 200. ISSN 1664-3224
Abstract
The IL-1 family member cytokine IL-36γ is recognised as key mediator in the immunopathology of psoriasis, hallmarks of which involve the activation of both resident and infiltrating inflammatory myeloid cells and aberrant angiogenesis. This research demonstrates a role for IL-36γ in both myeloid activation and angiogenesis. We show that IL-36γ induces the production of psoriasis-associated cytokines from macrophages (IL-23 and TNFα) and that this response is enhanced in macrophages from psoriasis patients. This effect is specific for IL-36γ and could not be mimicked by other IL-1 family cytokines such as IL-1α. IL-36γ was also demonstrated to induce endothelial tube formation and branching, in a VEGF-A-dependent manner. Furthermore, IL-36γ-stimulated macrophages potently activated endothelial cells and led to increased adherence of monocytes, effects that were markedly more pronounced for psoriatic macrophages. Interestingly, regardless of stimulus, psoriasis monocytes showed increased adherence to both the stimulated and unstimulated endothelium when compared with monocytes from healthy individuals. Collectively, these findings show that IL-36γ has the potential to enhance endothelium directed leucocyte infiltration into the skin and strengthen the IL-23/IL-17 pathway adding to the growing evidence of pathogenetic roles for IL-36γ in psoriatic responses. Our findings also point to a cellular response, which could potentially explain cardiovascular comorbidities in psoriasis in the form of endothelial activation and increased monocyte adherence.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2018 Bridgewood, Fearnley, Berekmeri, Laws, Macleod, Ponnambalam, Stacey, Graham and Wittmann. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
Keywords: | psoriasis; IL-36 gamma; IL-23; macrophages; monocytes; angiogenesis; endothelial; inflammation |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Biological Sciences (Leeds) > School of Molecular and Cellular Biology (Leeds) > Cardiovascular Science (Leeds) |
Funding Information: | Funder Grant number British Skin Foundation (Office 216) 5035s MRC MR/M01942X/1 |
Depositing User: | Symplectic Publications |
Date Deposited: | 27 Mar 2018 10:41 |
Last Modified: | 27 Mar 2018 10:52 |
Status: | Published |
Publisher: | Frontiers Media |
Identification Number: | 10.3389/fimmu.2018.00200 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:129019 |