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

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

PROVIDER: PRJNA1019390 | ENA |

REPOSITORIES: ENA

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

Project description: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.

2023-10-31 | GSE243690 | GEO

Human skin CD141<sup>+</sup> dendritic cells regulate cutaneous immunity via the neuropeptide urocortin 2.

Project description: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.

| S-EPMC10583083 | biostudies-literature

Co-expression of CD163 and CD141 Identifies Human Circulating IL-10-Producing Dendritic Cells (DC-10) [expression array]

Project description:Tolerogenic dendritic cells (DC) are key players in maintaining immunological homeostasis, dampening immune reactions, and promoting tolerance. DC-10, a tolerogenic population of human IL-10-producing DC characterized by the expression of HLA-G and ILT4, play a pivotal role in promoting tolerance via T regulatory type 1 (Tr1) cells. Thus far, the absence of specific biomarkers that uniquely identify DC-10 limited their studies in vivo. By gene expression profiling of in vitro differentiated human DC, we identified CD141 and CD163 as specific surface markers for DC-10. The co-expression of CD141 and CD163 in combination with CD14 and CD16 enables the ex vivo isolation of blood circulating DC-10. FACS-isolated CD14+CD16+CD141+CD163+ cells (ex vivo DC-10) from peripheral blood of healthy subjects produced spontaneously and upon activation IL-10 and limited levels of IL-12. Moreover, in vitro stimulation of allogeneic naive CD4+ T cells with ex vivo isolated CD14+CD16+CD141+CD163+ cells induced the differentiation of allo-specific Tr1 cells. Finally, ex vivo isolated CD14+CD16+CD141+CD163+ cells and in vitro differentiated DC-10 exhibited a similar transcriptional profile, characterized by anti-inflammatory and pro-tolerogenic signature. These results provide new insight into the DC-10 phenotype and on the role of circulating DC-10 in modulating T cell responses and promoting Tr1 cells. These findings open the opportunity to track DC-10 in vivo and to define their role in physiological and pathological settings.

2019-06-07 | GSE117946 | GEO

Co-expression of CD163 and CD141 Identifies Human Circulating IL-10-Producing Dendritic Cells (DC-10) [RNA-seq]

2019-06-07 | GSE117945 | GEO

Gene expression profiling of plasmacytoid dendritic cells from cutaneous lymph nodes

Project description:Plasmacytoid dendritic cells wre isolated from cutaneous lymph nodes of control C57BL/6 mice and used for microarray analysis.

2017-02-14 | GSE74276 | GEO

Gene expression profile of CD141+DNGR-1+ dendritic cells (cDC1s) derived in vitro from multipotent lymphoid progenitors (MLP) or common myeloid progenitors (CMP)

Project description:CD141+DNGR-1+ cDC1 have a dual origin. Both MLP and CMP can differentiate in CD141+DNGR-1+ cDC1s. Using Affymetrix microarrays (GeneChip Human Gene 2.0 ST) we compared gene expression of CD141+DNGR-1+ cDC1s originating either from MLPs or CMPs

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Transcriptomics profiling of CD141+ dendritic cells isolated from peripheral blood or synovial fluid of arthritis patients

Project description:Total RNA sequencing was performed on CD141+ DC isloated from peripheral blood of healthy individuals (n=5) or synovial fluid of patients with inflammatory arthritis (n=6)

2020-05-15 | GSE98950 | GEO

Transcriptomics profiling of CD141+ dendritic cells isolated from peripheral blood or synovial fluid of arthritis patients

Project description:Total RNA sequencing was performed on CD141+ DC isolated from peripheral blood of healthy individuals (n=4), synovial fluid of patients with inflammatory arthritis (n=5) and peripheral blood of patients with inflammatory arthritis (n=7). Cd1c+ DC were also sequenced from peripheral blood of healthy individuals (n=3).

2018-12-15 | GSE108174 | GEO

Transcriptomics profiling of CD141+ dendritic cells isolated from peripheral blood or synovial fluid of arthritis patients

Project description:Transcriptomics profiling of CD141+ dendritic cells isolated from peripheral blood or synovial fluid of arthritis patients

| PRJNA422753 | ENA

Co-expression of CD163 and CD141 Identifies Human Circulating IL-10-Producing Dendritic Cells (DC-10)

Project description:Co-expression of CD163 and CD141 Identifies Human Circulating IL-10-Producing Dendritic Cells (DC-10)

| PRJNA483777 | ENA