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JNK1 Signaling Downstream of the EGFR Pathway Contributes to Imiquimod-induced Skin Inflammation (RNA-seq)

ABSTRACT: 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.

ORGANISM(S): Mus musculus

PROVIDER: GSE164580 | GEO | 2021/01/12

REPOSITORIES: GEO

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JNK1 Signaling Downstream of the EGFR Pathway Contributes to Imiquimod-induced Skin Inflammation (ATAC-seq)

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.

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JNK1 Signaling Downstream of the EGFR Pathway Contributes to Imiquimod-induced Skin Inflammation

Project description:JNK1 Signaling Downstream of the EGFR Pathway Contributes to Imiquimod-induced Skin Inflammation

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JNK1 Signaling Downstream of the EGFR Pathway Contributes to Imiquimod-induced Skin Inflammation (ATAC-seq)

Project description:JNK1 Signaling Downstream of the EGFR Pathway Contributes to Imiquimod-induced Skin Inflammation (ATAC-seq)

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JNK1 Signaling Downstream of the EGFR Pathway Contributes to Imiquimod-induced Skin Inflammation (RNA-seq)

Project description:JNK1 Signaling Downstream of the EGFR Pathway Contributes to Imiquimod-induced Skin Inflammation (RNA-seq)

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Environmental factors transmitted by aryl hydrocarbon receptor influence severity of psoriatic skin inflammation [RNA-Seq]

Project description:Environmental stimuli are known to contribute to psoriasis pathogenesis and that of other autoimmune diseases, but the mechanism is unknown. Here we show that the aryl hydrocarbon receptor (AhR), a transcription factor that senses environmental stimuli, modulates pathology in psoriasis. AhR-activating ligands reduced inflammation in the lesional skin of psoriasis patients, whereas AhR antagonists upregulated inflammation. Similarly, AhR signaling via the endogenous FICZ ligand reduced the inflammatory response in the imiquimod-induced model of psoriasis and AhR deficient mice exhibited a substantial exacerbation of the disease, compared to AhR sufficient controls. Non-haematopoietic cells, in particular keratinocytes, were responsible for this hyper-inflammatory response, which involved increased reactivity to IL-1beta and upregulation of AP-1 family members of transcription factors. Thus, our data suggest a critical role for AhR in the regulation of inflammatory responses and open the possibility for novel therapeutic strategies in chronic inflammatory disorders. Total RNA obtained from skin explants taken from psoriatic patients or healthy donors cultured in the presence of AhR agonist or antagonist

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Next Generation Sequencing of wild type (WT) and K14 conditional Il9ra-/- mice ear epidermal cell layers

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