PuSH - Publication Server of Helmholtz Zentrum München

Wohn, C.* ; Ober-Blöbaum, J.L.* ; Haak, S. ; Pantelyushin, S.* ; Cheong, C.* ; Zahner, S.P.* ; Onderwater, S.* ; Kant, M.* ; Weighardt, H.* ; Holzmann, B.* ; Reizis, B.* ; Becher, B.* ; Prens, E.P.* ; Clausen, B.E.*

Langerinneg conventional dendritic cells produce IL-23 to drive psoriatic plaque formation in mice.

Proc. Natl. Acad. Sci. U.S.A. 110, 10723-10728 (2013)
Publ. Version/Full Text Volltext DOI PMC
Open Access Gold
Psoriasis is an autoinflammatory skin disease of unknown etiology. Topical application of Aldara cream containing the Toll-like receptor (TLR)7 agonist Imiquimod (IMQ) onto patients induces flares of psoriasis. Likewise, in mice IMQ triggers pathological changes closely resembling psoriatic plaque formation. Key cytokines like IL-23 and type-I IFN (IFN-I), both being produced mainly by dendritic cells (DCs), have been implicated in psoriasis. Although plasmacytoid DCs (pDCs) are the main source of IFNα and thought to initiate disease, conventional DCs (cDCs) appear to maintain the psoriatic lesions. Any role of cDCs during lesion formation remains elusive. Here, we report that selective activation of TLR7 signaling specifically in CD11c(+) DCs was sufficient to induce psoriasiform skin disease in mice. Intriguingly, both pDCs and the IFN-I pathway were dispensable for the development of local skin inflammation. Selective TLR7 triggering of Langerin(+) DCs resulted in attenuated disease, whereas their depletion did not alter the severity of skin lesions. Moreover, after IMQ-painting, IL-23 was exclusively produced by Langerin(neg) DCs in vivo. In conclusion, TLR7-activated Langerin(neg) cDCs trigger psoriatic plaque formation via IL-23-mediated activation of innate IL-17/IL-22-producing lymphocytes, independently of pDCs or IFN-I. These results suggest therapeutic targeting of IL-23 production by cDCs to refine current treatment strategies for psoriasis.
Impact Factor
Scopus SNIP
Web of Science
Times Cited
Scopus
Cited By
Altmetric
9.737
2.641
125
126
Tags
Annotations
Special Publikation
Hide on homepage

Edit extra information
Edit own tags
Private
Edit own annotation
Private
Hide on publication lists
on hompage
Mark as special
publikation
Publication type Article: Journal article
Document type Scientific Article
Keywords Delta T-cells ; Langerhans Cells ; Contact Hypersensitivity ; Antimicrobial Peptide ; Monoclonal-antibody ; Skin Inflammation ; Cutting Edge ; Imiquimod ; Expression ; Regulators
Language english
Publication Year 2013
HGF-reported in Year 2013
ISSN (print) / ISBN 0027-8424
e-ISSN 1091-6490
Quellenangaben Volume: 110, Issue: 26, Pages: 10723-10728 Article Number: , Supplement: ,
Publisher National Academy of Sciences
Reviewing status Peer reviewed
POF-Topic(s) 30202 - Environmental Health
Research field(s) Allergy
PSP Element(s) G-505400-001
PubMed ID 23754427
Scopus ID 84879547366
Erfassungsdatum 2013-08-01