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Skin single cell universe identifies IL-1B/IL23A co-producing CD14+ type 3 dendritic cells in psoriasis

ABSTRACT: Inflammatory skin diseases including atopic dermatitis (AD) and psoriasis (PSO) are underpinned by dendritic cell- (DC) mediated T cell responses. Currently, the heterogeneous human cutaneous DC population is incompletely characterized, and its contribution to these diseases remains unclear. Here, we performed index-sorted single-cell flow cytometry and RNA-sequencing of lesional and non-lesional AD and PSO skin to identify macrophages and all DC subsets, including the newly-described mature LAMP3+BIRC3+ DC enriched in immunoregulatory molecules (mregDC) and DC3. By integrating our indexed data with published skin datasets, we generated a myeloid cell universe of DC and macrophage subsets in healthy and diseased skin. Importantly, we found that CD14+ DC3 were increased in PSO lesional skin and co-produced IL1B and IL23A, which are pathologic in PSO. Our study comprehensively describes the molecular characteristics of macrophages and DC subsets in AD and PSO at single-cell resolution, and identifies CD14+ DC3 as potential promotors of inflammation in PSO.

ORGANISM(S): Homo sapiens

PROVIDER: GSE176509 | GEO | 2021/06/10

REPOSITORIES: GEO

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Project description:Dendritic cells (DC) are antigen presenting cells controlling T cell activation. In human, the diversity, ontogeny and functional capabilities of DC subsets are not fully understood. Here, we identified circulating CD88-CD1c+CD163+ DC (termed as DC3) as an immediate precursor of inflammatory CD88-CD14+CD1c+CD163+FcεRI+ DC. DC3 develop via a specific pathway, independent from the cDC-restricted (CDP) and monocyte-restricted (cMoP) progenitors, and are activated by GM-CSF. As classical DC, but unlike monocytes, DC3 drove the activation of naïve T cells. In vitro, DC3 displayed a distinctive ability to prime CD8+ T cells expressing a tissue-homing signature and the epithelial homing alpha-E integrin (CD103) through transforming growth factor-b (TGF-β) signaling. In vivo, DC3 infiltrated luminal breast cancer primary tumors and DC3 infiltration correlated positively with CD8+CD103+CD69+ tissue-resident memory T cells. Altogether, these findings define DC3 as a lineage of inflammatory DC endowed with a strong potential to regulate tumor immunity.

2020-05-23 | GSE151089 | GEO

Transcriptional and functional analysis of CD1c+ human dendritic cells identifies a CD163+ subset priming CD8+CD103+ T cells [Breast_iLN]

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2020-05-23 | GSE151072 | GEO

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2021-06-08 | GSE176279 | GEO

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2023-09-04 | GSE183047 | GEO

Expression data from primary human healthy donor-derived CD14- cDC2s, CD14+ cDC2s and monocytes

Project description:The human dendritic cell (DC) family has recently been expanded by CD1c+CD14+CD163+ DCs, introduced as DC3. DC3 are found in tumors and peripheral blood of cancer patients but which cells can serve as their pre-cursors remain unknown. CD1c+CD14+ cells share similarities with both CD1c+ DCs (cDC2s) and CD14+ monocytes on transcriptomic and phenotypic level. To investigate whether CD14+ cDC2s are closer related to CD14- cDC2s or monocytes on transcriptomic level, we analyzed their RNA.

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Single-cell transcriptome analysis of human skin identifies novel fibroblast subpopulation and enrichment of immune subsets in atopic dermatitis

Project description:Background: Atopic dermatitis (AD) is a prevalent inflammatory skin disease with a complex pathogenesis, involving immune cell and epidermal abnormalities. Despite whole tissue biopsy studies that have advanced the mechanistic understanding of AD, single-cell-based molecular alterations are largely unknown. Objective: To construct a detailed, high-resolution atlas of cell populations, and to assess variability in cell composition and cell-specific gene expression in the skin of AD patients versus controls. Methods: We performed single-cell RNA-sequencing on skin biopsies from 5 patients with AD (4 lesional samples, 5 non-lesional samples) and 7 healthy control subjects, using 10x Genomics. Results: We created transcriptomic profiles for 39,042 AD (lesional and non-lesional) and healthy skin cells. Fibroblasts demonstrated a novel COL6A5+COL18A1+ subpopulation that was unique to lesional AD, and expressed CCL2 and CCL19 cytokines. A corresponding LAMP3+ dendritic cell (DC) population that expressed the CCL19 receptor CCR7 was also unique to AD lesions, illustrating a potential role for fibroblast signaling to immune cells. Lesional AD samples were characterized by expansion of inflammatory DCs (CD1A+FCER1A+) and tissue resident memory T-cells (CD69+CD103+). The frequencies of type 2 (IL13+)/type 22 (IL22+) T-cells were higher than type 1 (IFNG+) in lesional AD, while this ratio was diminished slightly in non-lesional AD and further in controls. Conclusion: AD lesions were characterized by expanded type 2/type 22 T-cells and inflammatory DCs, and a unique inflammatory fibroblast that may interact with immune cells to regulate lymphoid cell organization and type 2 inflammation.

2020-03-24 | GSE147424 | GEO

Genomic Fingerprints of DC Subsets in the Human Vaginal Mucosa, Skin, and Blood

Project description:Dendritic cells (DC) localize throughout the body, where they sense and capture invading pathogens to induce protective immune responses. Hence, harnessing the biology of tissue-resident DC is crucial for the rational design of vaccines against pathogens. Herein, we characterized the transcriptomes of four antigen presenting cell (APC) subsets from the human vagina (vLC, vCD14- DC, vCD14+ DC, vMM-NM-&) and compared them to those of three skin DC (sDC) subsets and blood myeloid DC. We find that APC genomic fingerprints are significantly influenced by the tissue of origin as well as by individual APC subsets. Nonetheless, CD14+ APC from both vagina and skin are geared towards innate immunity and pro-inflammatory responses, whereas CD14- DC, particularly sLC, vLC, and vCD14- DC, display both Th2-inducing and regulatory phenotypes. We also identified vAPC subset-specific cellular and functional biomarkers that will guide the design of mucosal vaccines against sexually transmitted pathogens. Vaginal and skin tissues were obtained from female patients who underwent pelvic or cosmetic surgeries under protocols approved by the Institutional Review Board (IRB) of Baylor Research Institute (BRI). Patients were not infected with HIV, HCV or TB and did not display inflammation in the tissues. No other diagnosis information was available. Blood from healthy female volunteers was obtained under a protocol approved by the IRB of BRI. 87 total samples. 6 Blood mDC; 16 Dermal CD1c+CD14-; 10 Epidermal LC; 12 Vaginal CD1c+CD14-; 13 Vaginal CD1c+CD14+; 7 Vaginal HLADR- w/ 2 replicates (Vaginal HLADR-_VM610 and Vaginal HLADR-_VM611); 9Vaginal LC; 14 Vaginal Macrophage.

2014-12-17 | E-GEOD-54480 | biostudies-arrayexpress

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