Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Transcriptome of inflammatory myeloid DCs in psoriasis

ABSTRACT: Background: Previous work has identified CD11c+CD1c- dendritic cells (DCs) as the major ”inflammatory” dermal DC population in psoriasis vulgaris and CD1c+ DCs as the “resident” cutaneous DC population. Objective: To further define molecular differences between these two myeloid dermal DC populations. Methods: Inflammatory and resident DCs were single-cell sorted from psoriasis lesional skin biopsies, and gene array expression profiling was performed. Results were confirmed with RT-PCR, flow cytometry, immunohistochemistry, and double label immunofluorescence. Pooled human keratinocytes were cultured for functional studies. Results: TNF-related apoptosis-inducing ligand (TRAIL), Toll-like receptors (TLRs) 1 and 2, S100A12/EN-RAGE, CD32, and many other inflammatory products were selectively expressed in inflammatory DCs than in resident DCs. Flow cytometry and immunofluorescence confirmed higher protein expression on CD1c- versus CD1c+ DCs. TRAIL receptor, death receptor 4 (DR4), was expressed on basal keratinocytes and blood vessels, and in vitro culture of keratinocytes with rh-TRAIL induced CCL20 leukocyte chemokine. Conclusion: CD11c+CD1c- inflammatory DCs in psoriatic lesional skin express a wide range of inflammatory molecules compared to skin resident CD1c+ DCs. Some molecules made by inflammatory DCs, including TRAIL, could have direct effects on keratinocytes or other skin cell types to promote disease pathogenesis.

ORGANISM(S): Homo sapiens

PROVIDER: GSE20264 | GEO | 2010/05/24

SECONDARY ACCESSION(S): PRJNA124231

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Transcriptome of inflammatory myeloid DCs in psoriasis

Project description:Background: Previous work has identified CD11c+CD1c- dendritic cells (DCs) as the major 'inflammatory' dermal DC population in psoriasis vulgaris and CD1c+ DCs as the 'resident' cutaneous DC population. Objective: To further define molecular differences between these two myeloid dermal DC populations. Methods: Inflammatory and resident DCs were single-cell sorted from psoriasis lesional skin biopsies, and gene array expression profiling was performed. Results were confirmed with RT-PCR, flow cytometry, immunohistochemistry, and double label immunofluorescence. Pooled human keratinocytes were cultured for functional studies. Results: TNF-related apoptosis-inducing ligand (TRAIL), Toll-like receptors (TLRs) 1 and 2, S100A12/EN-RAGE, CD32, and many other inflammatory products were selectively expressed in inflammatory DCs than in resident DCs. Flow cytometry and immunofluorescence confirmed higher protein expression on CD1c- versus CD1c+ DCs. TRAIL receptor, death receptor 4 (DR4), was expressed on basal keratinocytes and blood vessels, and in vitro culture of keratinocytes with rh-TRAIL induced CCL20 leukocyte chemokine. Conclusion: CD11c+CD1c- inflammatory DCs in psoriatic lesional skin express a wide range of inflammatory molecules compared to skin resident CD1c+ DCs. Some molecules made by inflammatory DCs, including TRAIL, could have direct effects on keratinocytes or other skin cell types to promote disease pathogenesis. Shave biopsies were cultured overnight in dispase to remove the epidermis. Dermis was cultured for 36-48 hours to obtain dermal single cell suspensions. These cells were stained with HLA-DR, CD11c, BDCA-1 (DCs) and FACS-sorted into HLA-DR+11c+BDCA-1+, HLA-DR+11c+BDCA-1- populations into Trizol. RNA was extracted and processed for microarray. 2 dependent groups.

2010-06-08 | E-GEOD-20264 | biostudies-arrayexpress

Post-therapeutic relapse of psoriasis associated with CD11a blockade is associated with T cells and inflammatory myeloid DCs

Project description:To understand the development of new psoriasis lesions, we studied a group of moderate-to-severe psoriasis patients who experienced a relapse after ceasing efalizumab (anti-CD11a, Raptiva, Genentech). There were increased CD3+ T cells, neutrophils, CD11c+ and CD83+ myeloid DCs, but no increase in CD1c+ resident myeloid DCs. In relapsed lesions, there were many CD11c+CD1c-, inflammatory myeloid DCs identified by TNFSF10/TRAIL, TNF, and iNOS. CD11c+ cells in relapsed lesions co-expressed CD14 and CD16 in situ. Efalizumab induced an improvement in many psoriasis genes, and during relapse, the majority of these genes reversed back to a lesional state. Gene Set Enrichment Analysis (GSEA) of the transcriptome of relapsed tissue showed that many of the gene sets known to be present in psoriasis were also highly enriched in relapse. Hence, on ceasing efalizumab, T cells and myeloid cells rapidly enter the skin to cause classic psoriasis. To determine the transcsriptome of skin samples in 4 responding patients who relapsed after receiving efalizumab for treatment of psoriasis, using paired baseline non-lesional (NL, n=2); lesional (LS, n=4);week 12 post-treatment (week 12, n=4), and relapse (n=4). Comparison of mean gene expression of each group at baseline, and considering treatment effect

2012-01-30 | E-GEOD-30768 | biostudies-arrayexpress

Post-therapeutic relapse of psoriasis associated with CD11a blockade is associated with T cells and inflammatory myeloid DCs

2012-01-30 | GSE30768 | GEO

Single-cell genomics segregate different transcriptomic impacts of anti-IL-17A blockade on type 17 T-cells and regulatory immune cells in psoriasis skin

Project description:Durable psoriasis improvement has been reported in a subset of psoriasis patients after treatment withdrawal of biologics blocking IL-23/Type 17 T-cell (T17) autoimmune axis. However, it is not well understood if systemic blockade of the IL-23/T17 axis promotes immune tolerance in psoriasis skin. The purpose of the study was to find translational evidence that systemic IL-17A blockade promotes regulatory transcriptome modification in human psoriasis skin immune cell subsets. We analyzed human psoriasis lesional skin 6 mm punch biopsy tissues before and after systemic IL-17A blockade using the muti-genomics approach integrating immune cell-enriched scRNA-seq (n = 18), microarray (n = 61), and immunohistochemistry (n = 61) with repository normal control skin immune cell-enriched scRNA-seq (n = 10) and microarray (n = 8) data. For the T17 axis transcriptome, systemic IL-17A blockade depleted 100% of IL17A + T-cells and 95% of IL17F + T-cells in psoriasis skin. The expression of IL23A in DC subsets was also downregulated by IL-17A blockade. The expression of IL-17-driven inflammatory mediators (IL36G, S100A8, DEFB4A, and DEFB4B) in suprabasal keratinocytes was correlated with psoriasis severity and was downregulated by IL-17A blockade. For the regulatory DC transcriptome, the proportion of regulatory semimature DCs expressing regulatory DC markers of BDCA-3 (THBD) and DCIR (CLEC4A) was increased in posttreatment psoriasis lesional skin compared to pretreatment psoriasis lesional skin. In addition, IL-17A blockade induced higher expression of CD1C and CD14, which are markers of CD1c+ CD14+ dendritic cell (DC) subset that suppresses antigen-specific T-cell responses, in posttreatment regulatory semimature DCs compared to pretreatment regulatory semimature DCs. In conclusion, systemic IL-17A inhibition not only blocks the entire IL-23/T17 cell axis but also promotes regulatory gene expression in regulatory DCs in human psoriasis skin.

2023-09-04 | GSE183047 | GEO

A single intradermal injection of IFN-gamma induces a psoriasis-like state in both non-lesional psoriatic and healthy skin

Project description:Psoriasis is a chronic, debilitating, immune-mediated inflammatory skin disease. As IFN-gamma is involved in many cellular processes, including activation of T cells and dendritic cells (DCs), antigen processing and presentation, cell adhesion and trafficking, and cytokine and chemokine production, IFN-gamma-producing Th1 cells were proposed to be integral to the pathogenesis of psoriasis. Recently, IFN-gamma was shown to enhance IL-23 and IL-1 production by DCs and subsequently induce Th17 cells, important contributors to the inflammatory cascade in psoriasis lesions. To determine if IFN-gamma indeed induces the pathways leading to the development of psoriasis lesions, a single intradermal injection of IFN-gamma was administered to an area of clinically normal, non-lesional skin of psoriasis patients and biopsies were collected 24 hours later. Although there were no visible changes in the skin, IFN-gamma induced molecular and histological features characteristic of psoriasis lesions. IFN-gamma increased a number of differentially expressed genes in the skin, including many chemokines concomitant with an influx of T cells and inflammatory DCs. Furthermore, inflammatory DC products TNF, iNOS, IL-23, and TRAIL were present in IFN-gamma-treated skin. Thus, IFN-gamma, which is significantly elevated in non-lesional skin compared to healthy skin, appears to be a key pathogenic cytokine that can induce the inflammatory cascade in psoriasis. RNA was isolated from whole skin punch biopsies of either healthy or non-lesional psoraisis patients at baseline or 24 hours after placebo or IFN-g injection.

2011-11-30 | E-GEOD-32407 | biostudies-arrayexpress

A single intradermal injection of IFN-γ induces a psoriasis-like state in both non-lesional psoriatic and healthy skin

Project description:Psoriasis is a chronic, debilitating, immune-mediated inflammatory skin disease. As IFN-γ is involved in many cellular processes, including activation of T cells and dendritic cells (DCs), antigen processing and presentation, cell adhesion and trafficking, and cytokine and chemokine production, IFN-γ-producing Th1 cells were proposed to be integral to the pathogenesis of psoriasis. Recently, IFN-γ was shown to enhance IL-23 and IL-1 production by DCs and subsequently induce Th17 cells, important contributors to the inflammatory cascade in psoriasis lesions. To determine if IFN-γ indeed induces the pathways leading to the development of psoriasis lesions, a single intradermal injection of IFN-γ was administered to an area of clinically normal, non-lesional skin of psoriasis patients and biopsies were collected 24 hours later. Although there were no visible changes in the skin, IFN-γ induced molecular and histological features characteristic of psoriasis lesions. IFN-γ increased a number of differentially expressed genes in the skin, including many chemokines concomitant with an influx of T cells and inflammatory DCs. Furthermore, inflammatory DC products TNF, iNOS, IL-23, and TRAIL were present in IFN-γ-treated skin. Thus, IFN-γ, which is significantly elevated in non-lesional skin compared to healthy skin, appears to be a key pathogenic cytokine that can induce the inflammatory cascade in psoriasis.

2011-11-30 | GSE32407 | GEO

Human CD1c+ dendritic cells drive the differentiation of CD103+ CD8+ mucosal T cells via TGF-?

Project description:In comparison to murine dendritic cells (DCs), less is known about the function of human DCs in tissues. Here, we analyzed, using lung tissues from humans and humanized mice, the role of human CD1c+ and CD141+ DCs in determining the type of CD8+ T cell immunity to live-attenuated influenza virus (LAIV) vaccine. We found that both lung DC subsets acquired influenza antigens in vivo and expanded specific cytotoxic CD8+ T cells in vitro. However, lung-tissue-resident CD1c+ DCs but not CD141+ DCs were able to drive CD103 expression on CD8+ T cells and promote CD8+ T cell accumulation in lung epithelia in vitro and in vivo. CD1c+ DCs induction of CD103 expression was dependent on membrane-bound TGF-?1. Thus, CD1c+ and CD141+ DCs generate CD8+ T cells with different properties, and CD1c+ DCs specialize in the regulation of mucosal CD8+ T cells. Total RNA were isolated from purified human CD1c+ (BDCA1+) and CD141+ (BDCA3+) mDCs sorted from different tissues, including human blood, spleen and lungs of humanized mice, and human lungs. Eighteen samples in total were analyzed from different donors and tissues.

2013-04-04 | E-GEOD-43184 | biostudies-arrayexpress

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

Human CD1c+ dendritic cells drive the differentiation of CD103+ CD8+ mucosal T cells via TGF-β

Project description:In comparison to murine dendritic cells (DCs), less is known about the function of human DCs in tissues. Here, we analyzed, using lung tissues from humans and humanized mice, the role of human CD1c+ and CD141+ DCs in determining the type of CD8+ T cell immunity to live-attenuated influenza virus (LAIV) vaccine. We found that both lung DC subsets acquired influenza antigens in vivo and expanded specific cytotoxic CD8+ T cells in vitro. However, lung-tissue-resident CD1c+ DCs but not CD141+ DCs were able to drive CD103 expression on CD8+ T cells and promote CD8+ T cell accumulation in lung epithelia in vitro and in vivo. CD1c+ DCs induction of CD103 expression was dependent on membrane-bound TGF-β1. Thus, CD1c+ and CD141+ DCs generate CD8+ T cells with different properties, and CD1c+ DCs specialize in the regulation of mucosal CD8+ T cells.

2013-04-04 | GSE43184 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data