Alleviating psoriatic skin inflammation through augmentation of Treg cells via CTLA-4 signaling peptide
Psoriasis is a chronic inflammatory skin disease characterized by hyperplasia of keratinocytes and immune cell infiltration. The IL-17-producing T cells play a key role in psoriasis pathogenesis, while regulatory T (Treg) cells are diminished during psoriatic inflammation. Current psoriasis treatmen...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-09-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1233514/full |
| _version_ | 1827807228115025920 |
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| author | Woo-Sung Lee Kyung-Ho Nam Jong Hoon Kim Won-Ju Kim Jeong Eun Kim Jeong Eun Kim Eui-Cheol Shin Eui-Cheol Shin Gil-Ran Kim Gil-Ran Kim Je-Min Choi Je-Min Choi Je-Min Choi Je-Min Choi |
| author_facet | Woo-Sung Lee Kyung-Ho Nam Jong Hoon Kim Won-Ju Kim Jeong Eun Kim Jeong Eun Kim Eui-Cheol Shin Eui-Cheol Shin Gil-Ran Kim Gil-Ran Kim Je-Min Choi Je-Min Choi Je-Min Choi Je-Min Choi |
| author_sort | Woo-Sung Lee |
| collection | DOAJ |
| description | Psoriasis is a chronic inflammatory skin disease characterized by hyperplasia of keratinocytes and immune cell infiltration. The IL-17-producing T cells play a key role in psoriasis pathogenesis, while regulatory T (Treg) cells are diminished during psoriatic inflammation. Current psoriasis treatments largely focus on IL-17 and IL-23, however, few studies have explored therapeutic drugs targeting an increase of Treg cells to control immune homeostasis. In this study, we investigated the effects of a cytotoxic T lymphocyte antigen-4 (CTLA-4) signaling peptide (dNP2-ctCTLA-4) in Th17, Tc17, γδ T cells, Treg cells in vitro and a mouse model of psoriasis. Treatment with dNP2-ctCTLA-4 peptide showed a significant reduction of psoriatic skin inflammation with increased Treg cell proportion and reduced IL-17 production by T cells, indicating a potential role in modulating psoriatic skin disease. We compared dNP2-ctCTLA-4 with CTLA-4-Ig and found that only dNP2-ctCTLA-4 ameliorated the psoriasis progression, with increased Treg cells and inhibited IL-17 production from γδ T cells. In vitro experiments using a T cell-antigen presenting cell co-culture system demonstrated the distinct mechanisms of dNP2-ctCTLA-4 compared to CTLA-4-Ig in the induction of Treg cells. These findings highlight the therapeutic potential of dNP2-ctCTLA-4 peptide in psoriasis by augmenting Treg/Teff ratio, offering a new approach to modulating the disease. |
| first_indexed | 2024-03-11T21:54:23Z |
| format | Article |
| id | doaj.art-0eed9f6b34d9431cbe564d0267be7c0a |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-03-11T21:54:23Z |
| publishDate | 2023-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-0eed9f6b34d9431cbe564d0267be7c0a2023-09-26T05:16:58ZengFrontiers Media S.A.Frontiers in Immunology1664-32242023-09-011410.3389/fimmu.2023.12335141233514Alleviating psoriatic skin inflammation through augmentation of Treg cells via CTLA-4 signaling peptideWoo-Sung Lee0Kyung-Ho Nam1Jong Hoon Kim2Won-Ju Kim3Jeong Eun Kim4Jeong Eun Kim5Eui-Cheol Shin6Eui-Cheol Shin7Gil-Ran Kim8Gil-Ran Kim9Je-Min Choi10Je-Min Choi11Je-Min Choi12Je-Min Choi13Department of Life Science, College of Natural Sciences, Hanyang University, Seoul, Republic of KoreaDepartment of Life Science, College of Natural Sciences, Hanyang University, Seoul, Republic of KoreaDepartment of Dermatology and Cutaneous Biology Research Institute, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of KoreaDepartment of Pediatrics, Stanford University School of Medicine, Stanford, CA, United StatesDepartment of Dermatology, Hanyang University College of Medicine, Seoul, Republic of KoreaHanyang Institute of Bioscience and Biotechnology, Hanyang University, Seoul, Republic of KoreaGraduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Republic of KoreaThe Center for Viral Immunology, Korea Virus Research Institute, Institute for Basic Science (IBS), Daejeon, Republic of KoreaDepartment of Life Science, College of Natural Sciences, Hanyang University, Seoul, Republic of KoreaResearch Institute for Natural Sciences, Hanyang University, Seoul, Republic of KoreaDepartment of Life Science, College of Natural Sciences, Hanyang University, Seoul, Republic of KoreaHanyang Institute of Bioscience and Biotechnology, Hanyang University, Seoul, Republic of KoreaResearch Institute for Natural Sciences, Hanyang University, Seoul, Republic of KoreaResearch Institute for Convergence of Basic Sciences, Hanyang University, Seoul, Republic of KoreaPsoriasis is a chronic inflammatory skin disease characterized by hyperplasia of keratinocytes and immune cell infiltration. The IL-17-producing T cells play a key role in psoriasis pathogenesis, while regulatory T (Treg) cells are diminished during psoriatic inflammation. Current psoriasis treatments largely focus on IL-17 and IL-23, however, few studies have explored therapeutic drugs targeting an increase of Treg cells to control immune homeostasis. In this study, we investigated the effects of a cytotoxic T lymphocyte antigen-4 (CTLA-4) signaling peptide (dNP2-ctCTLA-4) in Th17, Tc17, γδ T cells, Treg cells in vitro and a mouse model of psoriasis. Treatment with dNP2-ctCTLA-4 peptide showed a significant reduction of psoriatic skin inflammation with increased Treg cell proportion and reduced IL-17 production by T cells, indicating a potential role in modulating psoriatic skin disease. We compared dNP2-ctCTLA-4 with CTLA-4-Ig and found that only dNP2-ctCTLA-4 ameliorated the psoriasis progression, with increased Treg cells and inhibited IL-17 production from γδ T cells. In vitro experiments using a T cell-antigen presenting cell co-culture system demonstrated the distinct mechanisms of dNP2-ctCTLA-4 compared to CTLA-4-Ig in the induction of Treg cells. These findings highlight the therapeutic potential of dNP2-ctCTLA-4 peptide in psoriasis by augmenting Treg/Teff ratio, offering a new approach to modulating the disease.https://www.frontiersin.org/articles/10.3389/fimmu.2023.1233514/fullpsoriasisdNP2-ctCTLA-4CTLA-4-IgTreg cellsIL-17A |
| spellingShingle | Woo-Sung Lee Kyung-Ho Nam Jong Hoon Kim Won-Ju Kim Jeong Eun Kim Jeong Eun Kim Eui-Cheol Shin Eui-Cheol Shin Gil-Ran Kim Gil-Ran Kim Je-Min Choi Je-Min Choi Je-Min Choi Je-Min Choi Alleviating psoriatic skin inflammation through augmentation of Treg cells via CTLA-4 signaling peptide Frontiers in Immunology psoriasis dNP2-ctCTLA-4 CTLA-4-Ig Treg cells IL-17A |
| title | Alleviating psoriatic skin inflammation through augmentation of Treg cells via CTLA-4 signaling peptide |
| title_full | Alleviating psoriatic skin inflammation through augmentation of Treg cells via CTLA-4 signaling peptide |
| title_fullStr | Alleviating psoriatic skin inflammation through augmentation of Treg cells via CTLA-4 signaling peptide |
| title_full_unstemmed | Alleviating psoriatic skin inflammation through augmentation of Treg cells via CTLA-4 signaling peptide |
| title_short | Alleviating psoriatic skin inflammation through augmentation of Treg cells via CTLA-4 signaling peptide |
| title_sort | alleviating psoriatic skin inflammation through augmentation of treg cells via ctla 4 signaling peptide |
| topic | psoriasis dNP2-ctCTLA-4 CTLA-4-Ig Treg cells IL-17A |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1233514/full |
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