Human skin CD141+ dendritic cells regulate cutaneous immunity via the neuropeptide urocortin 2
Summary: Skin immune homeostasis is a multi-faceted process where dermal dendritic cells (DDCs) are key in orchestrating responses to environmental stressors. We have previously identified CD141+CD14+ DDCs as a skin-resident immunoregulatory population that is vitamin-D3 (VitD3) inducible from monoc...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-10-01
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| Series: | iScience |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004223021065 |
| _version_ | 1797647844243406848 |
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| author | Prudence PokWai Lui Chrysanthi Ainali Chung-Ching Chu Manuela Terranova-Barberio Panagiotis Karagiannis Angela Tewari Niloufar Safinia Ehsan Sharif-Paghaleh Sophia Tsoka Grzegorz Woszczek Paola Di Meglio Giovanna Lombardi Antony R. Young Frank O. Nestle Niwa Ali |
| author_facet | Prudence PokWai Lui Chrysanthi Ainali Chung-Ching Chu Manuela Terranova-Barberio Panagiotis Karagiannis Angela Tewari Niloufar Safinia Ehsan Sharif-Paghaleh Sophia Tsoka Grzegorz Woszczek Paola Di Meglio Giovanna Lombardi Antony R. Young Frank O. Nestle Niwa Ali |
| author_sort | Prudence PokWai Lui |
| collection | DOAJ |
| description | Summary: Skin immune homeostasis is a multi-faceted process where dermal dendritic cells (DDCs) are key in orchestrating responses to environmental stressors. We have previously identified CD141+CD14+ DDCs as a skin-resident immunoregulatory population that is vitamin-D3 (VitD3) inducible from monocyte-derived DCs (moDCs), termed CD141hi VitD3 moDCs. We demonstrate that CD141+ DDCs and CD141hi VitD3 moDCs share key immunological features including cell surface markers, reduced T cell stimulation, IL-10 production, and a common transcriptomic signature. Bioinformatic analysis identified the neuroactive ligand receptor pathway and the neuropeptide, urocortin 2 (UCN2), as a potential immunoregulatory candidate molecule. Incubation with VitD3 upregulated UCN2 in CD141+ DCs and UVB irradiation induced UCN2 in CD141+ DCs in healthy skin in vivo. Notably, CD141+ DDC generation of suppressive Tregs was dependent upon the UCN2 pathway as in vivo administration of UCN2 reversed skin inflammation in humanized mice. We propose the neuropeptide UCN2 as a novel skin DC-derived immunoregulatory mediator with a potential role in UVB and VitD3-dependent skin immune homeostasis. |
| first_indexed | 2024-03-11T15:22:25Z |
| format | Article |
| id | doaj.art-bfb8903d33a541d1b9febee12c9327fb |
| institution | Directory Open Access Journal |
| issn | 2589-0042 |
| language | English |
| last_indexed | 2024-03-11T15:22:25Z |
| publishDate | 2023-10-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj.art-bfb8903d33a541d1b9febee12c9327fb2023-10-28T05:09:21ZengElsevieriScience2589-00422023-10-012610108029Human skin CD141+ dendritic cells regulate cutaneous immunity via the neuropeptide urocortin 2Prudence PokWai Lui0Chrysanthi Ainali1Chung-Ching Chu2Manuela Terranova-Barberio3Panagiotis Karagiannis4Angela Tewari5Niloufar Safinia6Ehsan Sharif-Paghaleh7Sophia Tsoka8Grzegorz Woszczek9Paola Di Meglio10Giovanna Lombardi11Antony R. Young12Frank O. Nestle13Niwa Ali14Peter Gorer Department of Immunobiology, School of Immunology and Microbial Science, King’s College London, London, UK; Centre for Gene Therapy and Regenerative Medicine, School of Basic and Biomedical Sciences, King’s College London, London, UKSt. John’s Institute of Dermatology, King’s College London and NIHR Biomedical Research Centre, London, UKSt. John’s Institute of Dermatology, King’s College London and NIHR Biomedical Research Centre, London, UKSt. John’s Institute of Dermatology, King’s College London and NIHR Biomedical Research Centre, London, UKSt. John’s Institute of Dermatology, King’s College London and NIHR Biomedical Research Centre, London, UKSt. John’s Institute of Dermatology, King’s College London and NIHR Biomedical Research Centre, London, UKInstitute of Liver Studies, Department of Inflammation Biology, School of Immunology and Microbial Sciences, James Black Centre, King’s College London, London, UKDepartment of Imaging Chemistry & Biology, School of Biomedical Engineering & Imaging Sciences, Faculty of Life Sciences & Medicine, King’s College London, London, UKDepartment of Informatics, Faculty of Natural, Mathematical and Engineering Sciences, King’s College London, Bush House, London, UKAsthma UK Centre in Allergic Mechanisms of Asthma, School of Immunology and Microbial Sciences, King’s College London, London, UKSt. John’s Institute of Dermatology, King’s College London and NIHR Biomedical Research Centre, London, UKPeter Gorer Department of Immunobiology, School of Immunology and Microbial Science, King’s College London, London, UKSt. John’s Institute of Dermatology, King’s College London and NIHR Biomedical Research Centre, London, UKSt. John’s Institute of Dermatology, King’s College London and NIHR Biomedical Research Centre, London, UKPeter Gorer Department of Immunobiology, School of Immunology and Microbial Science, King’s College London, London, UK; Centre for Gene Therapy and Regenerative Medicine, School of Basic and Biomedical Sciences, King’s College London, London, UK; St. John’s Institute of Dermatology, King’s College London and NIHR Biomedical Research Centre, London, UK; Corresponding authorSummary: Skin immune homeostasis is a multi-faceted process where dermal dendritic cells (DDCs) are key in orchestrating responses to environmental stressors. We have previously identified CD141+CD14+ DDCs as a skin-resident immunoregulatory population that is vitamin-D3 (VitD3) inducible from monocyte-derived DCs (moDCs), termed CD141hi VitD3 moDCs. We demonstrate that CD141+ DDCs and CD141hi VitD3 moDCs share key immunological features including cell surface markers, reduced T cell stimulation, IL-10 production, and a common transcriptomic signature. Bioinformatic analysis identified the neuroactive ligand receptor pathway and the neuropeptide, urocortin 2 (UCN2), as a potential immunoregulatory candidate molecule. Incubation with VitD3 upregulated UCN2 in CD141+ DCs and UVB irradiation induced UCN2 in CD141+ DCs in healthy skin in vivo. Notably, CD141+ DDC generation of suppressive Tregs was dependent upon the UCN2 pathway as in vivo administration of UCN2 reversed skin inflammation in humanized mice. We propose the neuropeptide UCN2 as a novel skin DC-derived immunoregulatory mediator with a potential role in UVB and VitD3-dependent skin immune homeostasis.http://www.sciencedirect.com/science/article/pii/S2589004223021065Immunology |
| spellingShingle | Prudence PokWai Lui Chrysanthi Ainali Chung-Ching Chu Manuela Terranova-Barberio Panagiotis Karagiannis Angela Tewari Niloufar Safinia Ehsan Sharif-Paghaleh Sophia Tsoka Grzegorz Woszczek Paola Di Meglio Giovanna Lombardi Antony R. Young Frank O. Nestle Niwa Ali Human skin CD141+ dendritic cells regulate cutaneous immunity via the neuropeptide urocortin 2 iScience Immunology |
| title | Human skin CD141+ dendritic cells regulate cutaneous immunity via the neuropeptide urocortin 2 |
| title_full | Human skin CD141+ dendritic cells regulate cutaneous immunity via the neuropeptide urocortin 2 |
| title_fullStr | Human skin CD141+ dendritic cells regulate cutaneous immunity via the neuropeptide urocortin 2 |
| title_full_unstemmed | Human skin CD141+ dendritic cells regulate cutaneous immunity via the neuropeptide urocortin 2 |
| title_short | Human skin CD141+ dendritic cells regulate cutaneous immunity via the neuropeptide urocortin 2 |
| title_sort | human skin cd141 dendritic cells regulate cutaneous immunity via the neuropeptide urocortin 2 |
| topic | Immunology |
| url | http://www.sciencedirect.com/science/article/pii/S2589004223021065 |
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