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Interleukin-26 potentiates type 2 skin inflammation in presence of interleukin-1β

ABSTRACT: Atopic dermatitis (AD) is a debilitating inflammatory skin disorder. Biologics targeting the IL-4/IL-13 axis are effective in AD, but there is still a large proportion of patients that do not respond to IL-4R blockade. Further exploration of potentially pathogenic T cell-derived cytokines in AD may lead to new effective treatments. This study aimed to investigate the downstream effects of IL-26 on skin in the context of type 2 skin inflammation. We found that IL-26 alone exhibited limited inflammatory activity in skin. However, in presence of IL-1β, IL-26 potentiated the secretion of TSLP, CXCL1 and CCL20 from human epidermis through JAK/STAT signaling. Moreover, in an in vivo AD-like skin inflammation model, IL-26 exacerbated skin pathology and locally increased type 2 cytokines, most notably of Il13 in skin T helper cells. Neutralization of IL-1β abrogated IL-26-mediated effects, indicating that the presence of IL-1β is required for full IL-26 downstream action in vivo. These findings suggest that the presence of IL-1β enables IL-26 to be a key amplifier of inflammation in the skin. As such, IL-26 may contribute to the development and pathogenesis of inflammatory skin disorders such as AD.

ORGANISM(S): Mus musculus

PROVIDER: GSE228860 | GEO | 2024/01/10

REPOSITORIES: GEO

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recombinant human epidermal model LC-MS/MS

Project description:Atopic dermatitis (AD) is a serious inflammatory skin disorder characterized by increased levels of proinflammatory cytokines that contribute to a vicious cycle of inflammation. While the in-flammatory recombinant human epidermal (RHE) models related to AD have been established, there is currently lack of comprehensive understanding. To reveal the alterations and identify potential hub genes in AD-related inflammation, related RHE models induced by inflammatory cocktail (polyinosinic-polycytidylic acid, TNF-α, IL-4 and IL-13) are constructed and analyzed through TMT-proteomic in combination with RNA-seq transcriptomic.

2023-08-07 | PXD043085 | Pride

Integrated proteomic analysis of Tumor Necrosis Factor α and Interleukin 1 β-induced endothelial inflammation

Project description:Objective The vascular endothelium provides a unique interaction plane for plasma proteins and leukocytes in inflammation. It has been established that particular proteins, including ICAM1, VCAM1 and SELE, are upregulated on the endothelial cell surface in the presence of pro-inflammatory cytokines Tumor Necrosis Factor α (TNFα) and Interleukin 1β (IL-1β). We now map cytokine-induced proteomic alterations to gain further insight into endothelial inflammation. Approach and results We evaluated alterations in the in-depth proteome, cell surface proteome and phosphoproteome after 24 hours of cytokine stimulation. In addition, protein expression profiles were measured after 4, 8, 16 and 24 hours of stimulation. We found that cytokine-stimulation induced a two-step response. After 4 hours, initial protein alterations were detected, including upregulation of ICAM1 and SELE, followed by a second burst of regulation after 8 to 16 hours, which included proteins involved in antigen processing, cytokine production, virus defense and ECM-interaction. Furthermore, we found that TNFα and IL-1β provoke a highly similar endothelial response with few specific alterations. Using a novel cell surface proteomics approach, we observed highly similar changes on the cell surface. Two surface proteins displayed altered labeling of specific epitopes, suggesting that these sites are modified or involved in interactions. Combined, our integrated proteomic data describes a full array of affected processes: leukocyte interaction, self-antigen presentation, cytokine production, nitric oxide production and extracellular matrix interaction. Conclusions Our study provides a detailed quantitative proteomic analysis of endothelial inflammation in which novel inflammation-responsive proteins were uncovered, and a two-step cytokine response was identified.

2018-09-03 | PXD009174 | Pride

Interleukin 2 distinctly activates human basophils in skin disorders

Project description:Basophils are important effector cells in allergic inflammation, anti-parasitic immune response and skin disorders. A number of activators including interleukin 3 (IL-3) and IgE have been identified in the regulation of human basophils expressing mediators such as histamine and leukotriene C4 (LTC4) and cytokines, including IL-4 and IL-13. Human basophils express high levels of IL-2 receptors. However, the function of the IL-2 pathway in basophils remains unknown. Here, we identify that IL-2-stimulated human basophils in vitro express a variety of inflammatory cytokines and chemokines including IL-5, IL-13, GM-CSF and CCL-17. Of note, one of the top regulated cytokines, IL-5, was for the first time identified to be expressed in human basophils and was distinctly regulated by IL-2, independently of IL-3 and IgE. Immunofluorescence analysis of skin specimens from bullous pemphigoid and eczema revealed that infiltrating basophils in skin lesions widely express IL-5 and GM-CSF. Together, our findings reveal IL-2 as a novel regulator of human basophils to express IL-5 and GM-CSF in skin disorders. This adds a new layer to support the importance of basophils in skin disorders.

2018-10-01 | GSE74375 | GEO

Pro-inflammatory stimulation of human skin-derived precursor cells modulates several of their immunology-related pathways.

Project description:Human skin-derived precursor cells (hSKP) are a stem cell population that represents key candidates for cell based-therapy. Inflammation, however, is often present in situations where cellular replacement therapy is required. These inflammatory conditions, and more specifically the presence of the cytokine interferon (IFN)-γ, might result in an increase of MHC class II antigens in hSKP-derived grafts and facilitate their rejection. We used microarray analyses to confirm the activated status of the pro-inflammatory condition, induced by exposure to a cocktail of pro-inflammatory cytokines (IL-1β, IFN-γ, TNFα and IFN-α). Consequently, we investigated the modulation by inflammation of canonical pathways related to immunology in hSKP.

2014-03-03 | GSE48757 | GEO

Transcriptional response of confluent human umbilical vein endothelial cells to stimulation with the related cytokines interleukin-1b or interleukin-33.

Project description:The similar response of endothelial cells to exogenous IL-33 or IL-1β prompted us to compare the genome-wide transcription profile of confluent human umbilical vein endothelial cell (HUVEC) cultures after 4 hours exposure to IL-33 or IL-1β. Analysis of these data revealed a striking similarity in the transcriptional response to the two cytokines.

2013-03-05 | GSE37624 | GEO

Mechanisms of Chorioamnionitis-associated Preterm Birth: Interleukin 1 β inhibits Progesterone Receptor Expression in Decidual Cells

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2015-02-11 | GSE65835 | GEO

Polarizing Cytokines and Staphylococcus aureus Cooperatively Induce Atopic Dermatitis-Like Transcriptomes

Project description:Background: Atopic dermatitis (AD) is a common inflammatory skin disease with a TH2 immune polarity and is often colonized with Staphylococcus aureus. Despite recent advances in understanding Staphylococcus species infection and the impact of polar TH cytokines on the skin, the interactions between these factors in AD pathology are poorly understood. Methods: AD-related key immune biomarkers were measured by quantitative real-time PCR in human keratinocytes exposed heat-killed S. epidermidis or S. aureus with/without polar T-cell derived cytokines such as IFN-γ (TH1), IL-4/IL-13 (TH2), and IL-22 (TH22). Further analysis was performed by RNA-sequencing to define broader responses in both Staphylococcus species and polar cytokines. The similarity of gene expression patterns in AD skin lesions and stimulated keratinocytes was evaluated by gene-set variation analysis (GSVA). Results: Gene expression analysis exhibited distinct immune responses in keratinocytes depending on individual bacterial or polar cytokine exposure. Besides, numerous genes were synergistically upregulated by the combination exposure of bacteria and polar TH cytokines. Moreover, GSVA revealed that combined exposure of S. aureus and IL-4 + IL-13 exhibited significantly higher correlations with a genomic signature of AD skin lesions than their single exposure or combinations of other polar TH cytokines. Conclusions: Our findings provide novel insights into AD-related transcriptional activation and illustrate a potentially novel pathogenic function of S. aureus and IL-4/IL-13 interactions in AD.

2021-12-31 | GSE173902 | GEO

The human pancreatic islet transcriptome: impact of pro-inflammatory cytokines

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2012-03-09 | E-GEOD-35296 | biostudies-arrayexpress

Mouse immune cells response Interleukin-33 (IL-33) [nanostring]

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2020-08-21 | GSE153488 | GEO

Transcription profiling of skin from patients with moderate to severe atopic dermatitis before and after treatment with IL-4R? inhibitor dupilumab (REGN668/SAR231893)

Project description:Atopic dermatitis (AD) is the most common inflammatory skin disease, with high unmet need for new therapies that are safe for chronic use. Emerging data suggest that TH2-cytokines play important roles in a variety of allergic and atopic conditions, including asthma and AD. In early phase clinical trials, dupilumab (a fully human monoclonal antibody against IL-4R? that potently blocks IL-4 and IL-13 signaling) rapidly and markedly improved clinical measures in adults with either asthma (with elevated eosinophil counts) or moderate-to-severe AD. The pathomechanisms that may be impacted by IL-4/13 blockade in these disease settings have not yet been characterized in detail. Transcriptome analyses in pre- and post-treatment skin biopsies from patients with moderate-to-severe AD treated with dupilumab or placebo in two completed clinical trials 18 Patients with AD treated with dupilumab or placebo. 28 biopsies in lesional (LS) Skin (16 pre-treatment and 12 post-treatment). 12 biopsies in non-lesional (NL) Skin (7 pre-treatment and 5 post treatment)

2014-12-04 | E-GEOD-59294 | biostudies-arrayexpress

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