Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJDB16652 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| DRR503686_1.fastq.gz | Fastqsanger.gz | |||
| DRR503686_2.fastq.gz | Fastqsanger.gz | |||
| DRR503687_1.fastq.gz | Fastqsanger.gz | |||
| DRR503687_2.fastq.gz | Fastqsanger.gz | |||
| DRR503688_1.fastq.gz | Fastqsanger.gz |
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Project description:c-Jun N-terminal protein kinase 1 (JNK1) is involved in multiple biological processes but its implication in inflammatory skin diseases is still poorly defined. Herein, we studied the role of JNK1 in the context of imiquimod-induced skin inflammation. We observed that constitutive ablation of JNK1 reduced imiquimod-induced acanthosis and expression of inflammatory markers. Conditional deletion of JNK1 in myeloid cells led to reduced skin inflammation, a finding that was associated with impaired Aldara®-induced inflammasome activation in vitro. Next, we evaluated the specific role of JNK1 in epidermal cells. We observed a reduced imiquimod-induced acanthosis and keratinocytes proliferation despite similar levels of inflammatory markers. Transcriptomic and epigenomic analysis of keratinocytes revealed the potential involvement of JNK1 in the EGFR signaling pathway. Finally, we show that inhibition of the EGFR pathway reduced imiquimod-induced acanthosis. Taken together, these data indicate that JNK1 plays a dual role in the context of psoriasis by regulating the production of inflammatory cytokines by myeloid cells and the sensitivity of keratinocytes to EGFR ligands. These results suggest that JNK1 could represent a valuable therapeutic target in the context of psoriasis.
2021-01-12 | GSE164580 | GEO
Project description:c-Jun N-terminal protein kinase 1 (JNK1) is involved in multiple biological processes but its implication in inflammatory skin diseases is still poorly defined. Herein, we studied the role of JNK1 in the context of imiquimod-induced skin inflammation. We observed that constitutive ablation of JNK1 reduced imiquimod-induced acanthosis and expression of inflammatory markers. Conditional deletion of JNK1 in myeloid cells led to reduced skin inflammation, a finding that was associated with impaired Aldara®-induced inflammasome activation in vitro. Next, we evaluated the specific role of JNK1 in epidermal cells. We observed a reduced imiquimod-induced acanthosis and keratinocytes proliferation despite similar levels of inflammatory markers. Transcriptomic and epigenomic analysis of keratinocytes revealed the potential involvement of JNK1 in the EGFR signaling pathway. Finally, we show that inhibition of the EGFR pathway reduced imiquimod-induced acanthosis. Taken together, these data indicate that JNK1 plays a dual role in the context of psoriasis by regulating the production of inflammatory cytokines by myeloid cells and the sensitivity of keratinocytes to EGFR ligands. These results suggest that JNK1 could represent a valuable therapeutic target in the context of psoriasis.
2021-01-12 | GSE164579 | GEO
Project description:Investigation of ripk3-dependent IAV-induced genes
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Project description:Tumor necrosis factor receptor associated factor 6 (TRAF6) is an adaptor protein that regulates NF-κB and MAPK signaling pathway and is reported to affect immune response and cell death in immune cells. However, the roles of TRAF6 in epithelium have not been well investigated. Using a mouse model of imiquimod-induced psoriasis dermatitis, we show that TRAF6 in epithelial cells totally regulates IL-17-mediated inflammation in the skin. Mice lacking TRAF6 in keratinocytes were unable to activate dendritic cells and failed to produce IL-23 or initiate IL-17 production from γδ T cells at the imiquimod-treated sites. Subcutaneous administrations of IL-23 restored IL-17 production in the mutant animals, suggesting that the induction of IL-23 production is the major TRAF6-dependent contribution of keratinocytes to this process. Therefore, the epithelial TRAF6 signaling is supposed to play an essential role in instructing and propagating the cutaneous immune response. To broadly characterize the impact of the lack of TRAF6 in keratinocytes on the skin inflammation, we analyzed gene expression in IMQ-treated whole ears of Traf6EKO mice and Traf6f/f mice using a cDNA microarray.
2018-10-16 | GSE101077 | GEO
Project description:The epidermis, outermost layer of the skin, forms a barrier and is involved in innate and adaptive immunity in an organism. Keratinocytes participate in all these three protective processes. However, a regulator of keratinocyte protective responses against external dangers and stresses remains elusive. We found that upregulation of the orphan gene 2610528A11Rik was a common factor in the skin of mice with several types of inflammation. In the human epidermis, peptide expression of G protein-coupled receptor 15 ligand (GPR15L), encoded by the human ortholog C10orf99, was highly induced in the lesional skin of patients with atopic dermatitis or psoriasis. C10orf99 gene transfection into normal human epidermal keratinocytes (NHEKs) induced the expression of inflammatory mediators and reduced the expression of barrier-related genes. Gene ontology analyses showed its association with translation, mitogen-activated protein kinase (MAPK), mitochondria, and lipid metabolism. Treatment with GPR15L reduced the expression levels of filaggrin and loricrin in human keratinocyte 3D cultures. Instead, their expression levels in mouse primary cultured keratinocytes did not show significant differences between the wild-type and 2610528A11Rik deficient keratinocytes. Lipopolysaccharide-induced expression of Il1b and Il6 was less in 2610528A11Rik deficient mouse keratinocytes than in wild-type, and imiquimod-induced psoriatic dermatitis was blunted in 2610528A11Rik deficient mice. Furthermore, repetitive subcutaneous injection of GPR15L in mouse ears induced skin inflammation in a dose-dependent manner. These results suggest that C10orf99/GPR15L is a primary inducible regulator that reduces the barrier formation and induces the inflammatory response of keratinocytes.
2022-02-28 | GSE189751 | GEO
Project description:Oncogene-induced senescence in primary mouse keratinocytes
| PRJNA361124 | ENA
Project description:Psoriasis is an inflammatory disorder characterized by keratinocyte hyper-proliferation and Th17-type immune responses. However, the roles of bioactive lipids and the regulation of their biosynthesis in this chronic skin disease are not fully understood. Herein, we show that group IVE cytosolic phospholipase A2 (cPLA2epsilon/PLA2G4E) plays a counterregulatory role against psoriatic inflammation by producing the non-canonical anti-inflammatory lipid N-acylethanolamine (NAE). Lipidomics analysis of mouse skin revealed that NAE species and their precursors (N-acyl-phosphatidylethanolamine and glycerophospho-N-acylethanolamine) were robustly increased in parallel with the ongoing process of imiquimod (IMQ)-induced psoriasis, accompanied by a marked upregulation of cPLA2epsilon in epidermal keratinocytes. Genetic deletion of cPLA2epsilon/Pla2g4e exacerbated IMQ-induced ear swelling and psoriatic marker expression, with a dramatic reduction of NAE-related lipids in IMQ-treated, and even normal, skin. Stimulation of cultured human keratinocytes with psoriatic cytokines concomitantly increased PLA2G4E expression and NAE production, and supplementation with NAEs significantly attenuated the cytokine-induced upregulation of the psoriatic marker S100A9. Increased expression of cPLA2epsilon was also evident in the epidermis of psoriatic patients. These findings reveal for the first time the in vivo role of cPLA2epsilon, which is highly induced in the keratinocytes of the psoriatic skin, promotes the biosynthesis of NAE-related lipids, and contributes to limiting psoriatic inflammation.
2022-03-31 | GSE196431 | GEO
Project description:Purpose: The goal of this study is to assess the transcriptomic changes induced by the loss BCL10/MALT1 signaling in keratinocytes and ist effect on IL-17A stimulation Methods: Keratinocytes were isolated from newborn Bcl10+/− and Bcl10−/− mice, cultured for 5 days, stimulated with IL-17A for 5 hours and harvested for RNA isolation. mRNA profiles were generated by deep sequencing, using Illumina NextSeq 550. Results: as shown by Gene Set Enrichment Analysis, IL-17A stimulation induced significant enrichment of an IL17 signature defined by Chiricozzi et al (JID 2011) in both Bcl10+/− and Bcl10−/− murine keratinocytes. However, direct comparison of Bcl10+/− and Bcl10−/− keratinocytes demonstrated a stronger enrichment of this signature in Bcl10 competent keratinocytes than in Bcl10 deficient cells.
2022-01-08 | GSE185998 | GEO
Project description:Calcium/calmodulin-dependent protein kinase IV promotes imiquimod-induced psoriatic inflammation via macrophages and keratinocytes in mice
| PRJNA842416 | ENA
Project description:Complex interactions of keratinocytes with various cells like inflammatory cells and stromal cells contribute to the pathogenesis of chronic inflammatory dermatoses. In proinflammatory cytokines mediating such ill settings, interleukin (IL)-9 plays a pathological role in inflammatory dermatoses. However, IL-9-related mechanisms in such diseases are still incompletely understood. In this study, we established tamoxifen-induced keratinocyte-specific IL-9 receptor alpha-chain-deficient mice (K14CRE/ERTIl9ra∆/∆ mice) to examine the role of IL-9 in multicellular interactions under the condition of chronic skin inflammation. Studies using an imiquimod-induced psoriasis-like model showed that K14CRE/ERTIl9ra∆/∆ mice significantly reduced the severity of dermatitis and mast cell infiltration compared to K14WTIl9rafl/fl mice as controls. The transcriptome analyses of psoriasis-like lesions showed that the level of peptide tyrosine-tyrosine (Pyy), a member of neuropeptide Y family, was markedly downregulated in K14CRE/ERTIl9ra∆/∆ epidermis. Blockade of Pyy suppressed thickening of the epidermis and mast cell number in imiquimod-treated wild-type mice. Together with in vitro studies indicating a capacity of Pyy to induce IL-9 production and chemotactic activity of bone marrow-derived mast cells (BMMCs), these suggest that Pyy-mediated interplay of keratinocytes and mast cells induces psoriasiform inflammation. Further investigation focusing on the IL-9-Pyy axis would provide a new modality for treatment of chronic inflammatory dermatoses.
2022-08-09 | GSE190867 | GEO