IL-36γ Is a Strong Inducer of IL-23 in Psoriatic Cells and Activates Angiogenesis
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 act...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2018-02-01
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| Series: | Frontiers in Immunology |
| Subjects: | |
| Online Access: | http://journal.frontiersin.org/article/10.3389/fimmu.2018.00200/full |
| _version_ | 1818304658068733952 |
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| author | Charlie Bridgewood Gareth W. Fearnley Anna Berekmeri Anna Berekmeri Philip Laws Philip Laws Tom Macleod Sreenivasan Ponnambalam Martin Stacey Anne Graham Miriam Wittmann Miriam Wittmann Miriam Wittmann |
| author_facet | Charlie Bridgewood Gareth W. Fearnley Anna Berekmeri Anna Berekmeri Philip Laws Philip Laws Tom Macleod Sreenivasan Ponnambalam Martin Stacey Anne Graham Miriam Wittmann Miriam Wittmann Miriam Wittmann |
| author_sort | Charlie Bridgewood |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-13T06:14:11Z |
| format | Article |
| id | doaj.art-18b2841b2c65416fa826a005d1348c64 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-13T06:14:11Z |
| publishDate | 2018-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-18b2841b2c65416fa826a005d1348c642022-12-21T23:57:00ZengFrontiers Media S.A.Frontiers in Immunology1664-32242018-02-01910.3389/fimmu.2018.00200305217IL-36γ Is a Strong Inducer of IL-23 in Psoriatic Cells and Activates AngiogenesisCharlie Bridgewood0Gareth W. Fearnley1Anna Berekmeri2Anna Berekmeri3Philip Laws4Philip Laws5Tom Macleod6Sreenivasan Ponnambalam7Martin Stacey8Anne Graham9Miriam Wittmann10Miriam Wittmann11Miriam Wittmann12Centre of Skin Sciences, School of Chemistry and Biosciences, University of Bradford, Bradford, United KingdomEndothelial Cell Biology Unit, School of Molecular and Cellular Biology, University of Leeds, Leeds, United KingdomDepartment of Dermatology, Chapel Allerton Hospital, Leeds, United KingdomFaculty of Biological Sciences, School of Molecular and Cellular Biology, University of Leeds, Leeds, United KingdomDepartment of Dermatology, Chapel Allerton Hospital, Leeds, United KingdomNational Institute of Health Research (NIHR), Leeds Biomedical Research Centre (BRC), Chapel Allerton Hospital, Leeds, United KingdomFaculty of Biological Sciences, School of Molecular and Cellular Biology, University of Leeds, Leeds, United KingdomEndothelial Cell Biology Unit, School of Molecular and Cellular Biology, University of Leeds, Leeds, United KingdomFaculty of Biological Sciences, School of Molecular and Cellular Biology, University of Leeds, Leeds, United KingdomBiomedical Sciences, School of Chemistry and Biosciences, University of Bradford, Bradford, United KingdomCentre of Skin Sciences, School of Chemistry and Biosciences, University of Bradford, Bradford, United KingdomNational Institute of Health Research (NIHR), Leeds Biomedical Research Centre (BRC), Chapel Allerton Hospital, Leeds, United KingdomLeeds Institute of Rheumatic and Musculoskeletal Medicine (LIRMM), University of Leeds, Leeds, United KingdomThe 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.http://journal.frontiersin.org/article/10.3389/fimmu.2018.00200/fullpsoriasisIL-36γIL-23macrophagesmonocytesangiogenesis |
| spellingShingle | Charlie Bridgewood Gareth W. Fearnley Anna Berekmeri Anna Berekmeri Philip Laws Philip Laws Tom Macleod Sreenivasan Ponnambalam Martin Stacey Anne Graham Miriam Wittmann Miriam Wittmann Miriam Wittmann IL-36γ Is a Strong Inducer of IL-23 in Psoriatic Cells and Activates Angiogenesis Frontiers in Immunology psoriasis IL-36γ IL-23 macrophages monocytes angiogenesis |
| title | IL-36γ Is a Strong Inducer of IL-23 in Psoriatic Cells and Activates Angiogenesis |
| title_full | IL-36γ Is a Strong Inducer of IL-23 in Psoriatic Cells and Activates Angiogenesis |
| title_fullStr | IL-36γ Is a Strong Inducer of IL-23 in Psoriatic Cells and Activates Angiogenesis |
| title_full_unstemmed | IL-36γ Is a Strong Inducer of IL-23 in Psoriatic Cells and Activates Angiogenesis |
| title_short | IL-36γ Is a Strong Inducer of IL-23 in Psoriatic Cells and Activates Angiogenesis |
| title_sort | il 36γ is a strong inducer of il 23 in psoriatic cells and activates angiogenesis |
| topic | psoriasis IL-36γ IL-23 macrophages monocytes angiogenesis |
| url | http://journal.frontiersin.org/article/10.3389/fimmu.2018.00200/full |
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