Original Research ARTICLE
IL-36γ is a strong inducer of IL-23 production and angiogenesis in psoriasis
- 1School of Chemistry and Biosciences, University of Bradford, United Kingdom
- 2School of Molecular & Cellular Biology, University of Leeds, United Kingdom
- 3Department of Dermatology, Chapel Allerton Hospital, United Kingdom
- 4School of Molecular and Cellular Biology, University of Leeds, United Kingdom
- 5Leeds Biomedical Research Centre, National Institute of Health Research (NIHR), United Kingdom
- 6School of Chemistry and Biosciences, University of Bradford, United Kingdom
- 7Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, United Kingdom
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, 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 to monocytes from healthy individuals. Collectively, these findings show that IL-36γ has the potential to enhance endothelium directed leukocyte 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.
Keywords: Psoriasis, IL-36γ, IL-23, Macrophages, Monocytes, Angiogenesis, endothelial, Inflammation.
Received: 08 Sep 2017;
Accepted: 23 Jan 2018.
Edited by:Eva Reali, I.R.C.C.S Istituto Ortopedico Galeazzi, Italy
Reviewed by:Angelo A. Manfredi, Vita-Salute San Raffaele University, Italy
Anna Balato, University of Naples Federico II, Italy
Copyright: © 2018 Bridgewood, Fearnley, Keszegpal, 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.
Dr. Anne Graham, University of Bradford, School of Chemistry and Biosciences, Bradford, United Kingdom, A.Graham@bradford.ac.uk
Dr. Miriam Wittmann, University of Leeds, Leeds Institute of Rheumatic and Musculoskeletal Medicine, Leeds, United Kingdom, M.Wittmann@leeds.ac.uk