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)
    
    
    
      
      
	
	    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.
	
	
	    
	
       
      
	
	    
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        Publication type
        Article: Journal article
    
 
    
        Document type
        Scientific Article
    
 
    
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        Keywords
        Delta T-cells ; Langerhans Cells ; Contact Hypersensitivity ; Antimicrobial Peptide ; Monoclonal-antibody ; Skin Inflammation ; Cutting Edge ; Imiquimod ; Expression ; Regulators
    
 
    
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        Language
        english
    
 
    
        Publication Year
        2013
    
 
    
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        HGF-reported in Year
        2013
    
 
    
    
        ISSN (print) / ISBN
        0027-8424
    
 
    
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        1091-6490
    
 
    
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	    Volume: 110,  
	    Issue: 26,  
	    Pages: 10723-10728 
	    Article Number: ,  
	    Supplement: ,  
	
    
 
    
        
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            National Academy of Sciences
        
 
        
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        Reviewing status
        Peer reviewed
    
 
     
    
        POF-Topic(s)
        30202 - Environmental Health
    
 
    
        Research field(s)
        Allergy	
    
 
    
        PSP Element(s)
        G-505400-001
    
 
    
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        Erfassungsdatum
        2013-08-01