Human skin CD141+ dendritic cells regulate cutaneous immunity via the neuropeptide urocortin 2

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

iScience (Oct 2023)

Human skin CD141+ dendritic cells regulate cutaneous immunity via the neuropeptide urocortin 2

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

Affiliations

Prudence PokWai Lui: Peter 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
Chrysanthi Ainali: St. John’s Institute of Dermatology, King’s College London and NIHR Biomedical Research Centre, London, UK
Chung-Ching Chu: St. John’s Institute of Dermatology, King’s College London and NIHR Biomedical Research Centre, London, UK
Manuela Terranova-Barberio: St. John’s Institute of Dermatology, King’s College London and NIHR Biomedical Research Centre, London, UK
Panagiotis Karagiannis: St. John’s Institute of Dermatology, King’s College London and NIHR Biomedical Research Centre, London, UK
Angela Tewari: St. John’s Institute of Dermatology, King’s College London and NIHR Biomedical Research Centre, London, UK
Niloufar Safinia: Institute of Liver Studies, Department of Inflammation Biology, School of Immunology and Microbial Sciences, James Black Centre, King’s College London, London, UK
Ehsan Sharif-Paghaleh: Department of Imaging Chemistry & Biology, School of Biomedical Engineering & Imaging Sciences, Faculty of Life Sciences & Medicine, King’s College London, London, UK
Sophia Tsoka: Department of Informatics, Faculty of Natural, Mathematical and Engineering Sciences, King’s College London, Bush House, London, UK
Grzegorz Woszczek: Asthma UK Centre in Allergic Mechanisms of Asthma, School of Immunology and Microbial Sciences, King’s College London, London, UK
Paola Di Meglio: St. John’s Institute of Dermatology, King’s College London and NIHR Biomedical Research Centre, London, UK
Giovanna Lombardi: Peter Gorer Department of Immunobiology, School of Immunology and Microbial Science, King’s College London, London, UK
Antony R. Young: St. John’s Institute of Dermatology, King’s College London and NIHR Biomedical Research Centre, London, UK
Frank O. Nestle: St. John’s Institute of Dermatology, King’s College London and NIHR Biomedical Research Centre, London, UK
Niwa Ali: Peter 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 author

Journal volume & issue: Vol. 26, no. 10
p. 108029

Abstract

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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.

Immunology

Published in iScience

ISSN: 2589-0042 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Science
Website: http://www.cell.com/iscience/home

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