Psoriatic skin inflammation is promoted by c-Jun/AP-1 dependent CCL2 and IL-23 expression in Dendritic cells

ABSTRACT: Toll-like receptor (TLR) stimulation induces innate immune responses involved in many inflammatory disorders including psoriasis. Although activation of the AP-1 transcription factor complex is common in TLR signaling, the specific involvement and induced targets remain poorly understood. Here, we investigated the role of c-Jun/AP-1 protein in skin inflammation following TLR7 activation using human psoriatic skin, Dendritic Cells (DC) and genetically engineered mouse models. We show that c-Jun regulates CCL2 production in DCs leading to impaired recruitment of plasmacytoid DCs to inflamed skin after treatment with the TLR7/8 agonist Imiquimod. Furthermore, deletion of c-Jun in DCs or chemical blockade of JNK/c-Jun signaling ameliorates psoriasis-like skin inflammation by reducing IL-23 pro

SUBMITTER: Philipp Novoszel 

PROVIDER: S-SCDT-EMM-2020-12409 | biostudies-other |

REPOSITORIES: biostudies-other