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

Authors :
Lui PP
Ainali C
Chu CC
Terranova-Barberio M
Karagiannis P
Tewari A
Safinia N
Sharif-Paghaleh E
Tsoka S
Woszczek G
Di Meglio P
Lombardi G
Young AR
Nestle FO
Ali N
Source :
IScience [iScience] 2023 Sep 26; Vol. 26 (10), pp. 108029. Date of Electronic Publication: 2023 Sep 26 (Print Publication: 2023).
Publication Year :
2023

Abstract

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 <superscript>+</superscript> CD14 <superscript>+</superscript> DDCs as a skin-resident immunoregulatory population that is vitamin-D <subscript>3</subscript> (VitD3) inducible from monocyte-derived DCs (moDCs), termed CD141 <superscript>hi</superscript> VitD3 moDCs. We demonstrate that CD141 <superscript>+</superscript> DDCs and CD141 <superscript>hi</superscript> 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 <superscript>+</superscript> DCs and UVB irradiation induced UCN2 in CD141 <superscript>+</superscript> DCs in healthy skin in vivo. Notably, CD141 <superscript>+</superscript> 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.<br />Competing Interests: F.O.N. is an employee of Sanofi, USA, and C.C.C. is an employee of Unilever, China.<br /> (© 2023 The Authors.)

Details

Language :
English
ISSN :
2589-0042
Volume :
26
Issue :
10
Database :
MEDLINE
Journal :
IScience
Publication Type :
Academic Journal
Accession number :
37860766
Full Text :
https://doi.org/10.1016/j.isci.2023.108029