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 LangerinnegDCs in vivo. In conclusion, TLR7-activated LangerinnegcDCs 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.

adaptive immunity, animal cell, animal experiment, article, controlled study, cytokine production, cytokine release, cytokine response, dendritic cell, disease severity, gene expression, in vivo study, mouse, nonhuman, phenotype, plaque forming cell, priority journal, promoter region, signal transduction, upregulation,
Proceedings of the National Academy of Sciences of the United States of America
Erasmus MC: University Medical Center Rotterdam

Wohn, C.T, Ober-Blöbaum, J.L, Haak, S, Pantelyushin, S, Cheong, C, Zahner, S.P, … Clausen, B.E. (2013). Langerinneg conventional dendritic cells produce IL-23 to drive psoriatic plaque formation in mice. Proceedings of the National Academy of Sciences of the United States of America, 110(26), 10723–10728. doi:10.1073/pnas.1307569110