Allergic contact dermatitis to nickel is characterized by a specific microRNA signature
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus Rattus norvegicus Homo sapiens
PROVIDER: GSE58817 | GEO | 2015/10/01
SECONDARY ACCESSION(S): PRJNA253662
REPOSITORIES: GEO
Similar Datasets
Project description:We found that peripheral blood mononuclear cells (PBMCs) (from subjects with allergy to nickel) stimulated with nickel were characterized by a specific miRNA signature that were different from vehicle-stimulated PBMCs.
2015-10-01 | GSE58815 | GEO
Project description:Our findings demonstrate that nickel-challenged skin in subjects with allergy to nickel is characterized by a specific miRNA signature compared to vehicle-challenged skin. In addition, we found that miRNA expression changes are different in allergic contact dermatitis (ACD to nickel) compared to irritant contact dermatitis (ICD).
2015-10-01 | GSE58814 | GEO
Project description:We found that keratinocytes (KCs) (from healthy subjects) stimulated with nickel were characterized by a specific miRNA signature that were different from vehicle-stimulated KCs.
2015-10-01 | GSE58816 | GEO
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Project description:The cytokine IL-9, derived primarily from T-helper 9 (Th9) lymphocytes, promotes expansion of the Th2 subset and is implicated in the mechanisms of allergic asthma. We hypothesize that IL-9 also has a role in human allergic contact dermatitis (ACD). To investigate this hypothesis, skin biopsy specimens of positive patch-test sites from non-atopic patients were assayed using quantitative PCR and immunohistochemistry. The cytokines IFN-γ, IL-4, IL-17A, IL-9, and PU.1, a Th9 associated transcription factor, were elevated when compared with paired normal skin. Immunohistochemistry on ACD skin biopsies identified PU.1+ CD3+ and PU.1+ CD4+ cells, consistent with Th9 lymphocytes, in the inflammatory infiltrate. Peripheral blood mononuclear cells from nickel-allergic patients, but not nonallergic controls, show significant IL-9 production in response to nickel. Blocking studies with mAbs to HLA-DR (but not HLA-A, -B, -C) or chloroquine significantly reduced this nickel-specific IL-9 production. In addition, blockade of IL-9 or IL-4 enhanced allergen-specific IFN-γ production. A contact hypersensitivity model using IL-9(-/-) mice shows enhanced Th1 lymphocyte immune responses, when compared with wild-type mice, consistent with our human in vitro data. This study demonstrates that IL-9, through its direct effects on Th1 and ability to promote IL-4 secretion, has a regulatory role for Th1 lymphocytes in ACD.
| S-EPMC4303591 | biostudies-literature
Project description:Allergic contact dermatitis (ACD) is well recognized as an adverse event associated with implantable medical devices that contain allergenic materials like nickel; however, other cutaneous consequences of chronic exposure to allergens in implanted devices are not well understood. Here, we present a clinical case of Marjolin's ulcer, an invasive squamous cell carcinoma (SCC) that developed in response to chronic ACD caused by an orthopedic implant. We used a standard murine model of contact hypersensitivity to determine whether chronic ACD promotes skin carcinogenesis. Chronic application of 1-fluoro-2,4-dinitrobenzene (DNFB) to carcinogen-treated skin led to the development of papillomas and aggressive SCC. DNFB-driven chronic ACD was marked by type 2 inflammation, which mediated skin carcinogenesis, as mice unable to mount an inflammatory response were less likely to develop skin tumors. Importantly, we found similar tumor-promoting inflammation surrounding the SCC in our patient. Our findings demonstrate that chronic ACD caused by constant exposure to an allergen can promote tumorigenesis at skin sites with preexisting cancer-initiated cells. Moreover, our results suggest that patients with implantable devices placed in close proximity to the skin should be monitored for ACD and highlight the importance of patch testing prior to the placement of such devices.
| S-EPMC4347218 | biostudies-literature
Project description:Allergic contact dermatitis (ACD) is a common inflammatory skin disease with a prevalence of approximately 20% in the European population. ACD is caused by contact allergens that are reactive chemicals able to modify non-immunogenic self-proteins to become immunogenic proteins. The most frequent contact allergens are metals, fragrances, and preservatives. ACD clinically manifests as pruritic eczematous lesions, erythema, local papules, and oedema. ACD is a T cell-mediated disease, involving both CD4+ and CD8+ T cells. In addition, ?? T cells appear to play an important role in the immune response to contact allergens. However, it is debated whether ?? T cells act in a pro- or anti-inflammatory manner. A special subset of ?? T cells, named dendritic epidermal T cells (DETC), is found in the epidermis of mice and it plays an important role in immunosurveillance of the skin. DETC are essential in sensing the contact allergen-induced stressed environment. Thus, allergen-induced activation of DETC is partly mediated by numerous allergen-induced stress proteins expressed on the keratinocytes (KC). Several stress proteins, like mouse UL-16-binding protein-like transcript 1 (Mult-1), histocompatibility 60 (H60) and retinoic acid early inducible-1 (Rae-1) ?-? family in mice and major histocompatibility complex (MHC) class I-chain-related A (MICA) in humans, are upregulated on allergen-exposed KC. Allergen-induced stress proteins expressed on the KC are consequently recognized by NKG2D receptor on DETC. This review focuses on the role of ?? T cells in ACD, with DETC in the spotlight, and on the role of stress proteins in contact allergen-induced activation of DETC.
| S-EPMC7248261 | biostudies-literature
Project description:BACKGROUND:Long-term use of most immunosuppressants to treat allergic contact dermatitis (ACD) generates unavoidable severe side effects, warranting discovery or development of new immunosuppressants with good efficacy and low toxicity is urgently needed to treat this condition. Hispidulin, a flavonoid compound that can be delivered topically due to its favorable skin penetrability properties, has recently been reported to possess anti-inflammatory and immunosuppressive properties. However, no studies have investigated the effect of hispidulin on Th1 cell activities in an ACD setting. METHODS:A contact hypersensitivity (CHS) mouse model was designed to simulate human ACD. The immunosuppressive effect of hispidulin was investigated via ear thickness, histologic changes (i.e., edema and spongiosis), and interferon-gamma (IFN-?) gene expression in 1-fluoro-2,4-dinitrobenzene (DNFB)-sensitized mice. Cytotoxicity, total number of CD4+ T cells, and percentage of IFN-?-producing CD4+ T cells were also investigated in vitro using isolated CD4+ T cells from murine spleens. RESULTS:Topically applied hispidulin effectively inhibited ear swelling (as measured by reduction in ear thickness), and reduced spongiosis, IFN-? gene expression, and the number of infiltrated immune cells. The inhibitory effect of hispidulin was observed within 6?h after the challenge, and the observed effects were similar to those effectuated after dexamethasone administration. Hispidulin at a concentration up to 50??M also suppressed IFN-?-producing CD4+ T cells in a dose-dependent manner without inducing cell death, and without a change in total frequencies of CD4+ T cells among different concentration groups. CONCLUSION:The results of this study, therefore, suggest hispidulin as a novel compound for the treatment of ACD via the suppression of IFN-? production in Th1 cells.
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| S-EPMC8651521 | biostudies-literature
Project description:In brief, skin resident cells were isolated from ear skin of mice and 10x Genomics single cell RNAseq was applied to identify distinct cell populations. Low quality cells and outliers were discarded, and only ～27600 viable cells were used for downstream analysis. Unsupervised clustering and gene expression were visualized with the Seurat on R studio, and assignment of cell clusters was based on expression of validated marker genes. Subsequent in-depth analysis was assisted by GENE DENOVO Inc (Guangzhou, China). Overall, We found that hapten application in pre-sensitized mice resulted in rapid infiltration of IFNγ-producing T cells, IL4- and IL13-producing basophils, and IL1β-producing neutrophils and macrophages. Sc-RNAseq identified a cluster of dermal fibroblasts enriched with IFNγ pathway signature and expressed high level of Cxcl9/10. In vitro, IFNγ–primed dFBs shifted the T cell Th1/Th2 polarization balance towards the Th1 phenotype through a CXCR3-dependent mechanism. Topical application of birch sap extract selectively blocked T cell-dFB interaction, suppressed Th1 cell activation and alleviated skin inflammation in the ACD model.
2024-08-09 | GSE224848 | GEO