IL-9 in psoriasis: human endothelial cells and murine T cells
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ABSTRACT:
ORGANISM(S): Mus musculus Homo sapiens
PROVIDER: GSE312663 | GEO | 2025/12/26
REPOSITORIES: GEO
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Project description:Obesity is a risk factor for psoriasis and negatively influences the severity, treatment responsiveness, and systemic comorbidities of psoriasis. This study aimed to investigate comprehensive inflammatory changes in obesity-associated psoriasis using an obese mouse model of psoriasis induced by topical application of imiquimod or dermal injection of interleukin (IL)-23. Obese mice exhibited aggravated psoriatic dermatitis with pronounced systemic inflammatory responses when exposed to imiquimod. Notably, imiquimod-induced psoriatic dermatitis in obese mice significantly reduced fat mass. Further, pronounced monocyte–macrophage infiltration of perigonadal adipose tissue, increased expression of genes linked to inflammation, and upregulation of cell death-associated molecules were evident in obese mice treated with imiquimod compared with their lean counterparts. In contrast, IL-23 injection could induce similar features of psoriatic inflammation in obese and lean mice, without causing adipose tissue destruction or a systemic increase in inflammatory mediators. Obese adipose tissue of mice with imiquimod-induced psoriatic inflammation features genetic and epigenetic changes in adipocytes and shifts in macrophage compartments toward disturbed homeostasis using multiomic single-nucleus sequencing targeting RNA and accessible chromatin. Therefore, systemic manifestations of psoriasis, coupled with obesity-induced changes in adipose tissue, synergistically exacerbate psoriasis by disrupting the homeostatic microenvironments of adipose tissue.
2025-08-27 | GSE267866 | GEO
Project description:Obesity has been known to be associated with psoriasis, negatively affecting its prevalence, severity, and treatment response. However, a detailed systemic inflammatory microenvironment in obesity-associated psoriasis has not been extensively investigated. To explore this further, we used a mouse model of psoriasis induced by topical application of imiquimod or injection of IL-23. We found that obese mice exhibited systemic inflammatory responses when exposed to imiquimod, with increased expression of inflammatory cytokines in the skin and elevated serum levels of mediators implicated in psoriasis pathogenesis. Notably, imiquimod also caused a significant decrease in body weight and fat, which was more pronounced in obese mice, resulting a thinner subcutaneous fat layer. Further analysis revealed higher macrophage infiltration, upregulated genes relating to the inflammatory response, and increased expression of necrosis-associated molecules in the perigonadal fat of imiquimod-treated obese mice than in lean mice. IL-23 injection induced comparable pathogenic features of psoriatic inflammation in obese and lean mice without causing adipose tissue destruction or systemic increase of inflammatory mediators.
2025-07-31 | GSE246074 | GEO
Project description:Psoriasis is a common inflammatory skin disease characterized by aberrant inflammation and epidermal hyperplasia. Molecular mechanisms that regulate psoriasis-like skin inflammation remain to be fully understood. Here we show that the expression of Ovol1 transcription factor is upregulated in psoriatic skin, and its deletion results in aggravated psoriasis-like skin symptoms following stimulation with imiquimod (IMQ). Using bulk and single-cell RNA-sequencing, we identify molecular changes in the epidermal, fibroblast and immune cells of Ovol1-deficient skin that reflect altered course of epidermal differentiation and enhanced inflammatory responses. Furthermore, we provide evidence for excessive full-length IL-1 signaling in the microenvironment of IMQ-treated Ovol1-deficient skin that functionally contributes to immune cell infiltration and epidermal hyperplasia. Collectively, our study uncovers a protective role for Ovol1 in curtailing psoriasis-like inflammation and the associated skin pathology
2021-12-01 | GSE159704 | GEO
Project description:Our group recently described a population of antigen presenting cells that appear to be critical in psoriasis pathogenesis, termed inflammatory myeloid dendritic cells (CD11c+ BDCA1-). Triggering receptor expressed on myeloid cells type-1 (TREM-1) signaling was a major canonical pathway in the published transcriptome of these cells. TREM-1 is a member of the immunoglobulin superfamily, active through the DAP12 signaling pathway, with an unknown ligand. Activation through TREM-1 induces inflammatory cytokines including IL-8, MCP/CCL2 and TNF. We now show that TREM-1 was expressed in the skin of healthy and psoriatic patients, and there was increased soluble TREM-1 in the circulation of psoriasis patients. In psoriasis lesions, TREM-1 was co-localized with dendritic cells as well as CD31+ endothelial cells. TREM-1 expression was reduced with successful NB-UVB, etanercept and anti-IL-17 treatments. An in vitro model of PGN-activated monocytes as inflammatory myeloid DCs was developed to study TREM-1 blockade, and treatment with a TREM-1 blocking chimera decreased allogeneic Th17 activation, as well as IL-17 production. Furthermore, TREM-1 blockade of ex vivo psoriatic dendritic cells in an alloMLR also showed a decrease in IL-17. Together, these data suggest that the TREM-1 signaling pathway offers a novel therapeutic target to prevent the effects of inflammatory myeloid DCs in psoriasis. Monocytes were isolated by plastic adherence, treated with TLR agonists overnight, washed twice and harvested in RTL-buffer. RNA was extracted and processed for microarray. 3 groups and 3 replicates with a paired structure across replicates
2012-11-17 | E-GEOD-42305 | biostudies-arrayexpress
Project description:Increased intestinal permeability can exacerbate psoriasis, a systemic inflammatory disease with complex pathogenesis. Using a mouse model of psoriasis elicited by the TLR7 ligand imiquimod, we found that psoriatic dermatitis was accompanied by small-intestinal inflammatory changes associated with eosinophil degranulation which led to impaired intestinal barrier integrity. Inflammatory responses in the skin and small intestine were accelerated in mice that are prone to eosinophil degranulation. Caco-2 human intestinal epithelial cells treated with media containing eosinophil granule proteins exhibited signs of inflammation and damage. Imiquimod-induced skin and intestinal inflammatory changes were attenuated in eosinophil-deficient mice, and this attenuation was counteracted by eosinophil transfer. Imiquimod levels and eosinophil distribution were positively correlated in the intestine. TLR7-deficient mice did not show intestinal eosinophil degranulation and exhibited attenuated skin and small-intestinal inflammation following imiquimod application. These results suggest a TLR7-dependent bidirectional skin-to-gut communication in psoriatic inflammation, and that intestinal inflammatory changes can accelerate psoriasis.
2024-04-30 | GSE237610 | GEO
Project description:Emerging evidence has shown that microbiota dysbiosis and aberrant bile acids (BAs) profiles are correlated with disease progression. This study elucidates dysregulated BAs metabolism in psoriasis patients and imiquimod-treated female mice, coupled with increased expression of the farnesoid X receptor (FXR) in keratinocytes. Activation of FXR by glycochenodeoxycholic acid (GCDCA) ameliorates psoriatic symptoms by enhancing lipid metabolism, particularly fatty acid oxidation. Mechanistically, the arrow_drop_downmore
2026-03-31 | MTBLS14191 | MetaboLights
Project description:The polyphenol resveratrol has anti-inflammatory effects in various cells, tissues, animals and human settings of low-grade inflammation. Psoriasis is a disease of both localized and systemic low-grade inflammation. The Sirtuin1 enzyme thought to mediate the effects of resveratrol is present in skin and resveratrol is known to downregulate NF-κB; a major contributor in the development of psoriasis. Consequently we investigated whether resveratrol has an effect on an Imiquimod induced psoriasis-like skin inflammation in mice and sought to identify candidate genes, pathways and interleukins mediating the observed effects. The study consisted of three treatment groups: A control group, an Imiquimod group and an Imiquimod+resveratrol group. Psoriasis severity was assessed using elements of the Psoriasis Area Severity Index, actual skin thickness measurements, and histological examination. We performed an RNA microarray from lesional skin and afterwards Ingenuity pathway analysis to identify affected signalling pathways. Our microarray was compared to a previously deposited microarray to determine if gene changes were psoriasis-like, and to a human microarray to determine if findings could be relevant in a human setting. Imiquimod treatment induced a psoriasis-like skin inflammation. Resveratrol significantly diminished the severity of the psoriasis-like skin inflammation. The RNA microarray revealed a psoriasis-like gene expression-profile in the Imiquimod treated group, and highlighted several resveratrol dependent changes in relevant genes, such as increased expression of genes associated with retinoic acid stimulation and reduced expression of genes involved in IL-17 dependent pathways (e.g.IL-17A, IL-17F,IL-23p19 ). Quantitative PCR confirmed a resveratrol dependent decrease in mRNA levels of IL-17A and IL-19; both central in developing psoriasis. In conclusion, resveratrol ameliorates psoriasis, and changes in expression of retinoic acid stimulated genes, IL-17 signalling pathways, IL-17A and IL-19 mRNA levels in a beneficial manner suggests it might have a role in the treatment of psoriasis and should be explored further in a human setting.
2015-11-17 | GSE63684 | GEO
Project description:Psoriasis is a chronic skin suffering with multiple comorbidities such as psoriatic arthritis and cardiovascular diseases. Increasing evidences have shown the γδ T cells as the sources of IL-17A play critical roles in the psoriatic syndrome. However, there is still lack an effective way to manipulate these pathogenic γδ T cells which were less studied relative to ab T cells. The present study aims to characterize the phenotype of γδ T cells and evaluate the impact of D-mannose (a C-2 epimer of glucose) on γδ T-mediated psoriasis. We found the psoriatic γδ T cells underwent robust proliferation and acquired an IL-17 producing phenotype. The transcriptomic profiles of these skin draining LN γδ T cells had elevated glycolytic features. Importantly, Treatment of D-mannose inhibited γδ T cells and successfully alleviated the local and systematic inflammations induced by imiquimod. The decreased AKT/mTOR/HIF-1a signaling and glycolytic ability may contribute to the suppression of γδ T cells achieved by mannose. Our study deepened the understandings of γδ T cells in psoriasis, meanwhile, promoted D-mannose utilization as a potent clinical application for γδ T cells driven autoimmune diseases.
2022-03-30 | GSE188905 | GEO
Project description:Background: Atherosclerotic cardiovascular disease (ASCVD) remains the leading cause of mortality in the western world despite the success of lipid lowering therapies, highlighting the need for novel lipid-independent therapeutic strategies. Genome-wide association studies (GWAS) have identified numerous genes associated with ASCVD that appear to predominantly function in the vessel wall, suggesting both that vascular cells mediate ASCVD, and that the genes and pathways essential for this vascular cell function may be novel therapeutic targets for the treatment of ASCVD. Furthermore, some of these implicated genes appear to function in the adventitial layer of the vasculature, suggesting these cells are able to potentiate ASCVD. Methods: To investigate the contribution of adventitial cells in atherosclerosis, we conducted single-cell RNA sequencing (scRNA-seq) of the aortic adventitia during atherogenesis in male Ldlr-/- mice via pools of three mice, two samples per condition. We cross-referenced the scRNA-seq data with human ASCVD GWAS to identify regulators of adventitial responses in ASCVD. These regulators were then validated in vitro in human adventitial fibroblasts. Results: We identified four adventitial fibroblast populations, all of which displayed shifts in population size and gene expression over the course of atherogenesis. SERPINH1, an ASCVD-linked GWAS gene, was differentially expressed in adventitial fibroblasts during atherogenesis. Knockdown of SERPINH1 in vitro reduced fibroblast migration and altered subcluster marker gene expression. Conclusions: These findings reveal dynamic changes in adventitial fibroblasts during atherosclerosis and suggest that reduced SERPINH1 expression disrupts adventitial fibroblast function, contributing to ASCVD progression.
2025-10-22 | GSE289281 | GEO
Project description:CaMK4 has an important function in autoimmune diseases, and the contribution of CaMK4 in psoriasis remains obscure. Here, we show that CaMK4 expression is significantly increased in psoriatic lesional skin from psoriasis patients compared to healthy human skin as well as inflamed skin from an imiquimod (IMQ)-induced mouse model of psoriasis compared to healthy mouse skin. Camk4-deficient (Camk4−/−) mice treated with IMQ exhibit reduced severity of psoriasis compared to wild-type (WT) mice. There are more macrophages and fewer IL-17A+γδ TCR+ cells in the skin of IMQ-treated Camk4−/− mice compared to IMQ-treated WT mice. CaMK4 inhibits IL-10 production by macrophages, thus allowing excessive psoriatic inflammation. Deletion of Camk4 in macrophages alleviates IMQ-induced psoriatic inflammation in mice. In keratinocytes, CaMK4 inhibits apoptosis as well as promotes cell proliferation and the expression of pro-inflammatory genes such as S100A8 and CAMP. Taken together, these data indicate that CaMK4 regulates IMQ-induced psoriasis by sustaining inflammation and provides a potential target for psoriasis treatment.
2022-05-28 | GSE204832 | GEO