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Human Skin CD141+ Dendritic Cells Regulate Cutaneous Immunity via the Neuropeptide Urocortin-2

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+CD14+DDCs as a skin-resident immunoregulatory population that is vitamin-D3(VitD3) inducible from monocyte-derived DCs(moDCs), termed CD141hiVitD3 moDCs. We demonstrate CD141+DDCs and CD141hiVitD3 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 up-regulated UCN2 in CD141+DCs and ultraviolet-B(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.

ORGANISM(S): Homo sapiens

PROVIDER: GSE243690 | GEO | 2023/10/31

REPOSITORIES: GEO

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