Yes / 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. / Faculty of Life Sciences, University of Bradford. MRC, Grant/Award Number: MR/M01942X/1; British Skin Foundation, Grant/Award Number: BSF 5035.
| Identifer | oai:union.ndltd.org:BRADFORD/oai:bradscholars.brad.ac.uk:10454/15260 |
| Date | 26 February 2018 |
| Creators | Bridgewood, Charlie, Fearnley, G.W., Berekmeri, A., Laws, P., Macleod, T., Ponnambalam, S., Stacey, M., Graham, Anne M, Wittman, Miriam |
| Source Sets | Bradford Scholars |
| Language | English |
| Detected Language | English |
| Type | Article, Published version |
| Rights | © 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., CC-BY |
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