Lui Prudence PokWai, Ainali Chrysanthi, Chu Chung-Ching, Terranova-Barberio Manuela, Karagiannis Panagiotis, Tewari Angela, Safinia Niloufar, Sharif-Paghaleh Ehsan, Tsoka Sophia, Woszczek Grzegorz, Di Meglio Paola, Lombardi Giovanna, Young Antony R, Nestle Frank O, Ali Niwa
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.
iScience. 2023 Sep 26;26(10):108029. doi: 10.1016/j.isci.2023.108029. eCollection 2023 Oct 20.
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 CD141CD14 DDCs as a skin-resident immunoregulatory population that is vitamin-D (VitD3) inducible from monocyte-derived DCs (moDCs), termed CD141 VitD3 moDCs. We demonstrate that CD141 DDCs and CD141 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 Notably, CD141 DDC generation of suppressive Tregs was dependent upon the UCN2 pathway as 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.
皮肤免疫稳态是一个多方面的过程，其中真皮树突状细胞（DDCs）在协调对环境应激源的反应中起关键作用。我们之前已将CD141⁺CD14⁻ DDCs鉴定为一种皮肤驻留免疫调节细胞群，它可由单核细胞来源的DCs（moDCs）经维生素D（VitD3）诱导产生，称为CD141 VitD3 moDCs。我们证明CD141 DDCs和CD141 VitD3 moDCs具有共同的关键免疫学特征，包括细胞表面标志物、降低的T细胞刺激、白细胞介素-10产生以及共同的转录组特征。生物信息学分析确定神经活性配体受体途径和神经肽尿皮质素2（UCN2）为潜在的免疫调节候选分子。用VitD3孵育可上调CD141 DCs中的UCN2，紫外线B（UVB）照射可诱导健康皮肤中CD141 DCs产生UCN2。值得注意的是，CD141 DDCs产生抑制性调节性T细胞（Tregs）依赖于UCN2途径，因为给予UCN2可逆转人源化小鼠的皮肤炎症。我们提出神经肽UCN2是一种新型的皮肤DC来源的免疫调节介质，在UVB和VitD3依赖性皮肤免疫稳态中具有潜在作用。
