Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Novoszel, P; Holcmann, M; Stulnig, G; De, Sa, Fernandes, C; Zyulina, V; Borek, I; Linder, M; Bogusch, A; Drobits, B; Bauer, T; Tam-Amersdorfer, C; Brunner, PM; Stary, G; Bakiri, L; Wagner, EF; Strobl, H; Sibilia, M.
Psoriatic skin inflammation is promoted by c-Jun/AP-1-dependent CCL2 and IL-23 expression in dendritic cells.
EMBO Mol Med. 2021; 13(4):e12409
Doi: 10.15252/emmm.202012409
[OPEN ACCESS]
Web of Science
PubMed
FullText
FullText_MUG
- Co-Autor*innen der Med Uni Graz
- Bauer Thomas
- Borek Izabela Malgorzata
- Strobl Herbert
- Stulnig Gabriel
- Tam-Amersdorfer Carmen
- Zyulina Victoria
- Altmetrics:
- Dimensions Citations:
- Plum Analytics:
- Scite (citation analytics):
- 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 production in DCs. Importantly, the control of IL-23 and CCL2 by c-Jun is most pronounced in murine type-2 DCs. CCL2 and IL-23 expression co-localize with c-Jun in type-2/inflammatory DCs in human psoriatic skin and JNK-AP-1 inhibition reduces the expression of these targets in TLR7/8-stimulated human DCs. Therefore, c-Jun/AP-1 is a central driver of TLR7-induced immune responses by DCs and JNK/c-Jun a potential therapeutic target in psoriasis.
- Find related publications in this database (using NLM MeSH Indexing)
- Animals - administration & dosage
- Dendritic Cells - administration & dosage
- Imiquimod - administration & dosage
- Inflammation - administration & dosage
- Interleukin-23 - administration & dosage
- Mice - administration & dosage
- Transcription Factor AP-1 - administration & dosage
- Find related publications in this database (Keywords)
- c‐
- Jun
- dendritic cells
- psoriasis
- targeted therapy
- TLR7