Langerin(neg) conventional dendritic cells produce IL-23 to drive psoriatic plaque formation in mice

Proc Natl Acad Sci U S A. 2013 Jun 25;110(26):10723-8. doi: 10.1073/pnas.1307569110. Epub 2013 Jun 10.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aminoquinolines / administration & dosage
  • Animals
  • Antigens, Surface / biosynthesis
  • Antigens, Surface / genetics*
  • Disease Models, Animal
  • Imiquimod
  • Interleukin-23 / biosynthesis*
  • Langerhans Cells / drug effects
  • Langerhans Cells / immunology*
  • Lectins, C-Type / biosynthesis
  • Lectins, C-Type / deficiency*
  • Lectins, C-Type / genetics*
  • Mannose-Binding Lectins / biosynthesis
  • Mannose-Binding Lectins / deficiency*
  • Mannose-Binding Lectins / genetics*
  • Membrane Glycoproteins / agonists
  • Mice
  • Mice, Knockout
  • Myeloid Differentiation Factor 88 / deficiency
  • Myeloid Differentiation Factor 88 / genetics
  • Myeloid Differentiation Factor 88 / immunology
  • Psoriasis / etiology
  • Psoriasis / immunology*
  • Psoriasis / pathology
  • Toll-Like Receptor 7 / agonists


  • Aminoquinolines
  • Antigens, Surface
  • Cd207 protein, mouse
  • Interleukin-23
  • Lectins, C-Type
  • Mannose-Binding Lectins
  • Membrane Glycoproteins
  • Myd88 protein, mouse
  • Myeloid Differentiation Factor 88
  • Tlr7 protein, mouse
  • Toll-Like Receptor 7
  • Imiquimod