The G Protein-Coupled Receptor (GPR) 15 Counteracts Antibody-Mediated Skin Inflammation
The G protein-coupled receptor 15 (GPR15) has recently been highlighted as an important regulator of T cell trafficking into the gut under physiological and pathophysiological conditions. Additionally, circumstantial evidence has accumulated that GPR15 may also play a role in the regulation of chron...
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Frontiers Media S.A.
2020-08-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fimmu.2020.01858/full |
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| author | Lina Jegodzinski Tanya Sezin Karin Loser Sadegh Mousavi Detlef Zillikens Detlef Zillikens Christian D. Sadik Christian D. Sadik |
| author_facet | Lina Jegodzinski Tanya Sezin Karin Loser Sadegh Mousavi Detlef Zillikens Detlef Zillikens Christian D. Sadik Christian D. Sadik |
| author_sort | Lina Jegodzinski |
| collection | DOAJ |
| description | The G protein-coupled receptor 15 (GPR15) has recently been highlighted as an important regulator of T cell trafficking into the gut under physiological and pathophysiological conditions. Additionally, circumstantial evidence has accumulated that GPR15 may also play a role in the regulation of chronic inflammation. However, the (patho)physiological significance of GPR15 has, in general, remained rather enigmatic. In the present study, we have addressed the role of GPR15 in the effector phase of autoantibody-mediated skin inflammation, specifically in the antibody transfer mouse model of bullous pemphigoid-like epidermolysis bullosa acquisita (BP-like EBA). Subjecting Gpr15−/− mice to this model, we have uncovered that GPR15 counteracts skin inflammation. Thus, disease was markedly aggravated in Gpr15−/− mice, which was associated with an increased accumulation of γδ T cells in the dermis. Furthermore, GPR15L, the recently discovered cognate ligand of GPR15, was markedly upregulated in inflamed skin. Collectively, our results highlight GPR15 as counter-regulator of neutrophilic, antibody-mediated cutaneous inflammation. Enhancing the activity of GPR15 may therefore constitute a novel therapeutic principle in the treatment of pemphigoid diseases, such as BP-like EBA. |
| first_indexed | 2024-12-14T04:10:03Z |
| format | Article |
| id | doaj.art-7363bb0489ac4a849f6aed995a6d622a |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-14T04:10:03Z |
| publishDate | 2020-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-7363bb0489ac4a849f6aed995a6d622a2022-12-21T23:17:42ZengFrontiers Media S.A.Frontiers in Immunology1664-32242020-08-011110.3389/fimmu.2020.01858548203The G Protein-Coupled Receptor (GPR) 15 Counteracts Antibody-Mediated Skin InflammationLina Jegodzinski0Tanya Sezin1Karin Loser2Sadegh Mousavi3Detlef Zillikens4Detlef Zillikens5Christian D. Sadik6Christian D. Sadik7Department of Dermatology, Allergy, and Venereology, University of Lübeck, Lübeck, GermanyDepartment of Dermatology, Allergy, and Venereology, University of Lübeck, Lübeck, GermanyDepartment of Dermatology, University of Münster, Münster, GermanyDepartment of Dermatology, Allergy, and Venereology, University of Lübeck, Lübeck, GermanyDepartment of Dermatology, Allergy, and Venereology, University of Lübeck, Lübeck, GermanyCenter for Research on Inflammation of the Skin, University of Lübeck, Lübeck, GermanyDepartment of Dermatology, Allergy, and Venereology, University of Lübeck, Lübeck, GermanyCenter for Research on Inflammation of the Skin, University of Lübeck, Lübeck, GermanyThe G protein-coupled receptor 15 (GPR15) has recently been highlighted as an important regulator of T cell trafficking into the gut under physiological and pathophysiological conditions. Additionally, circumstantial evidence has accumulated that GPR15 may also play a role in the regulation of chronic inflammation. However, the (patho)physiological significance of GPR15 has, in general, remained rather enigmatic. In the present study, we have addressed the role of GPR15 in the effector phase of autoantibody-mediated skin inflammation, specifically in the antibody transfer mouse model of bullous pemphigoid-like epidermolysis bullosa acquisita (BP-like EBA). Subjecting Gpr15−/− mice to this model, we have uncovered that GPR15 counteracts skin inflammation. Thus, disease was markedly aggravated in Gpr15−/− mice, which was associated with an increased accumulation of γδ T cells in the dermis. Furthermore, GPR15L, the recently discovered cognate ligand of GPR15, was markedly upregulated in inflamed skin. Collectively, our results highlight GPR15 as counter-regulator of neutrophilic, antibody-mediated cutaneous inflammation. Enhancing the activity of GPR15 may therefore constitute a novel therapeutic principle in the treatment of pemphigoid diseases, such as BP-like EBA.https://www.frontiersin.org/article/10.3389/fimmu.2020.01858/fullGPR15pemphigoid diseaseepidermolysis bullosa acquisitaautoantibodiesskin inflammationGPR15L |
| spellingShingle | Lina Jegodzinski Tanya Sezin Karin Loser Sadegh Mousavi Detlef Zillikens Detlef Zillikens Christian D. Sadik Christian D. Sadik The G Protein-Coupled Receptor (GPR) 15 Counteracts Antibody-Mediated Skin Inflammation Frontiers in Immunology GPR15 pemphigoid disease epidermolysis bullosa acquisita autoantibodies skin inflammation GPR15L |
| title | The G Protein-Coupled Receptor (GPR) 15 Counteracts Antibody-Mediated Skin Inflammation |
| title_full | The G Protein-Coupled Receptor (GPR) 15 Counteracts Antibody-Mediated Skin Inflammation |
| title_fullStr | The G Protein-Coupled Receptor (GPR) 15 Counteracts Antibody-Mediated Skin Inflammation |
| title_full_unstemmed | The G Protein-Coupled Receptor (GPR) 15 Counteracts Antibody-Mediated Skin Inflammation |
| title_short | The G Protein-Coupled Receptor (GPR) 15 Counteracts Antibody-Mediated Skin Inflammation |
| title_sort | g protein coupled receptor gpr 15 counteracts antibody mediated skin inflammation |
| topic | GPR15 pemphigoid disease epidermolysis bullosa acquisita autoantibodies skin inflammation GPR15L |
| url | https://www.frontiersin.org/article/10.3389/fimmu.2020.01858/full |
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