JNK1 (c-Jun N-terminal kinase 1) has been studied in numerous biological phenomena, but its role in skin inflammation diseases has not been fully defined yet. We therefore evaluated the role of JNK1 in imiquimod-induced dermatitis, a classical model that shares many features with human psoriasis. We showed that JNK1 was necessary for the expression of inflammatory markers and for acanthosis induced by imiquimod. We demonstrated that the loss of JNK1 in dendritic cells or myeloid cells reduced inflammatory markers but did not affect acanthosis induced by imiquimod. In vitro experiments in bone marrow-derived macrophages (BMMs) supported the role of JNK1 in the activation of the inflammasome pathway by the Aldara® cream. Next, we observed that the loss of JNK1 in keratinocytes did not reduce imiquimod-induced expression of most inflammatory markers but acanthosis and proliferation of epidermal cells was decreased. To better understand the role of JNK1 in keratinocytes, we evaluated the transcriptome and the epigenomic landscape of JNK1-deficient epidermal cells from mice treated with imiquimod. These data highlighted the potential role of JNK1 downstream of the EGFR pathway. We further observed that the inhibition of the EGFR pathway decreased imiquimod-induced acanthosis. Our work shows the dual role of JNK1 in skin inflammation induced by imiquimod. On one hand, JNK1 influences the expression of inflammatory mediators by myeloid cells, probably through the inflammasome pathway. On the other hand, JNK1 modulates the response of keratinocytes to EGFR ligands. Taken together, these data suggest that JNK1 could represent a valuable therapeutic target for the management of psoriasis. / Doctorat en Sciences médicales (Médecine) / info:eu-repo/semantics/nonPublished
| Identifer | oai:union.ndltd.org:ulb.ac.be/oai:dipot.ulb.ac.be:2013/314810 |
| Date | 01 December 2020 |
| Creators | Le, Aurore |
| Contributors | Goriely, Stanislas, Braun, Michel Y, Robaye, Bernard, Richert, Bertrand, Blanpain, Cédric, Pincelli, Carlo, Poumay, Yves |
| Publisher | Universite Libre de Bruxelles, Université libre de Bruxelles, Faculté de Médecine – Sciences médicales, Bruxelles |
| Source Sets | Université libre de Bruxelles |
| Language | English |
| Detected Language | English |
| Type | info:eu-repo/semantics/doctoralThesis, info:ulb-repo/semantics/doctoralThesis, info:ulb-repo/semantics/openurl/vlink-dissertation |
| Format | 3 full-text file(s): application/pdf | application/pdf | application/pdf |
| Rights | 3 full-text file(s): info:eu-repo/semantics/openAccess | info:eu-repo/semantics/openAccess | info:eu-repo/semantics/closedAccess |
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