Regulatory T Cells Restrain Pathogenic T Helper Cells during Skin Inflammation
Summary: Psoriasis is a chronic relapsing, remitting interleukin (IL)-23/IL-17-driven skin disease mediated by the interplay of T cells and polymorphonuclear granulocytes. Although preclinical studies have provided insights into the mechanisms of disease initiation, the underpinnings of natural dise...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2018-12-01
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| Series: | Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124718319235 |
| _version_ | 1818939583804473344 |
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| author | Tom Hartwig Pascale Zwicky Bettina Schreiner Nikhil Yawalkar Phil Cheng Alexander Navarini Reinhard Dummer Lukas Flatz Curdin Conrad Christoph Schlapbach Burkhard Becher |
| author_facet | Tom Hartwig Pascale Zwicky Bettina Schreiner Nikhil Yawalkar Phil Cheng Alexander Navarini Reinhard Dummer Lukas Flatz Curdin Conrad Christoph Schlapbach Burkhard Becher |
| author_sort | Tom Hartwig |
| collection | DOAJ |
| description | Summary: Psoriasis is a chronic relapsing, remitting interleukin (IL)-23/IL-17-driven skin disease mediated by the interplay of T cells and polymorphonuclear granulocytes. Although preclinical studies have provided insights into the mechanisms of disease initiation, the underpinnings of natural disease remission remain largely unknown. Here, we addressed the contribution of regulatory Foxp3+ T cells (Treg cells) in psoriasiform skin inflammation and remission using the Aldara-skin inflammation model in combination with the inducible depletion of Foxp3+ Treg cells. Loss of Treg cells exacerbated skin inflammation, but this did not involve increased γδ T cell expansion or the local production of the psoriasis-associated cytokines IL-17A, IL-17F, and IL-22, which are the main driving forces of disease development. Instead, Treg cells suppressed the infiltration of granulocyte-macrophage colony-stimulating factor (GM-CSF)-producing CD4+ T cells into the lesioned skin, and neutralizing GM-CSF in Treg cell-deficient mice reversed hyper-inflammation, resulting in disease regression. Therefore, we identified a non-redundant role of Treg cells restraining skin inflammation and mediating skin homeostasis. : The contribution of Treg cells to psoriasis is poorly understood. By combining inducible depletion of Treg cells with the Aldara model of psoriasiform inflammation, Hartwig et al. reveal a non-redundant role of Treg cells in promoting the remission of skin inflammation by limiting invasion of CD4+ GM-CSF-producing T cells into psoriatic skin. Keywords: psoriasis, melanoma, ipilimumab, Aldara, skin inflammation, Foxp3, Treg cells, CD4 T cells, GM-CSF |
| first_indexed | 2024-12-20T06:26:04Z |
| format | Article |
| id | doaj.art-8d9c187b76344a6880e7889d53095cd4 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-20T06:26:04Z |
| publishDate | 2018-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-8d9c187b76344a6880e7889d53095cd42022-12-21T19:50:17ZengElsevierCell Reports2211-12472018-12-01251335643572.e4Regulatory T Cells Restrain Pathogenic T Helper Cells during Skin InflammationTom Hartwig0Pascale Zwicky1Bettina Schreiner2Nikhil Yawalkar3Phil Cheng4Alexander Navarini5Reinhard Dummer6Lukas Flatz7Curdin Conrad8Christoph Schlapbach9Burkhard Becher10Institute of Experimental Immunology, Department of Inflammation Research, University of Zurich, 8057 Zurich, SwitzerlandInstitute of Experimental Immunology, Department of Inflammation Research, University of Zurich, 8057 Zurich, SwitzerlandInstitute of Experimental Immunology, Department of Inflammation Research, University of Zurich, 8057 Zurich, Switzerland; Department of Neurology, University Hospital Zurich, 8091 Zurich, SwitzerlandDepartment of Dermatology, Inselspital, University of Bern, 3010 Bern, SwitzerlandDepartment of Dermatology, University Hospital Zurich, 8091 Zurich, SwitzerlandDepartment of Dermatology, University Hospital Zurich, 8091 Zurich, SwitzerlandDepartment of Dermatology, University Hospital Zurich, 8091 Zurich, SwitzerlandDepartment of Dermatology and Allergology, Cantonal Hospital St. Gallen, St. Gallen, SwitzerlandDepartment of Dermatology, University Hospital CHUV, Lausanne 1011, SwitzerlandDepartment of Dermatology, Inselspital, University of Bern, 3010 Bern, SwitzerlandInstitute of Experimental Immunology, Department of Inflammation Research, University of Zurich, 8057 Zurich, Switzerland; Corresponding authorSummary: Psoriasis is a chronic relapsing, remitting interleukin (IL)-23/IL-17-driven skin disease mediated by the interplay of T cells and polymorphonuclear granulocytes. Although preclinical studies have provided insights into the mechanisms of disease initiation, the underpinnings of natural disease remission remain largely unknown. Here, we addressed the contribution of regulatory Foxp3+ T cells (Treg cells) in psoriasiform skin inflammation and remission using the Aldara-skin inflammation model in combination with the inducible depletion of Foxp3+ Treg cells. Loss of Treg cells exacerbated skin inflammation, but this did not involve increased γδ T cell expansion or the local production of the psoriasis-associated cytokines IL-17A, IL-17F, and IL-22, which are the main driving forces of disease development. Instead, Treg cells suppressed the infiltration of granulocyte-macrophage colony-stimulating factor (GM-CSF)-producing CD4+ T cells into the lesioned skin, and neutralizing GM-CSF in Treg cell-deficient mice reversed hyper-inflammation, resulting in disease regression. Therefore, we identified a non-redundant role of Treg cells restraining skin inflammation and mediating skin homeostasis. : The contribution of Treg cells to psoriasis is poorly understood. By combining inducible depletion of Treg cells with the Aldara model of psoriasiform inflammation, Hartwig et al. reveal a non-redundant role of Treg cells in promoting the remission of skin inflammation by limiting invasion of CD4+ GM-CSF-producing T cells into psoriatic skin. Keywords: psoriasis, melanoma, ipilimumab, Aldara, skin inflammation, Foxp3, Treg cells, CD4 T cells, GM-CSFhttp://www.sciencedirect.com/science/article/pii/S2211124718319235 |
| spellingShingle | Tom Hartwig Pascale Zwicky Bettina Schreiner Nikhil Yawalkar Phil Cheng Alexander Navarini Reinhard Dummer Lukas Flatz Curdin Conrad Christoph Schlapbach Burkhard Becher Regulatory T Cells Restrain Pathogenic T Helper Cells during Skin Inflammation Cell Reports |
| title | Regulatory T Cells Restrain Pathogenic T Helper Cells during Skin Inflammation |
| title_full | Regulatory T Cells Restrain Pathogenic T Helper Cells during Skin Inflammation |
| title_fullStr | Regulatory T Cells Restrain Pathogenic T Helper Cells during Skin Inflammation |
| title_full_unstemmed | Regulatory T Cells Restrain Pathogenic T Helper Cells during Skin Inflammation |
| title_short | Regulatory T Cells Restrain Pathogenic T Helper Cells during Skin Inflammation |
| title_sort | regulatory t cells restrain pathogenic t helper cells during skin inflammation |
| url | http://www.sciencedirect.com/science/article/pii/S2211124718319235 |
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