Langerinneg conventional dendritic cells produce IL-23 to drive psoriatic plaque formation in mice
| Autor: | Heike Weighardt, Boris Reizis, Errol P. Prens, Bernhard Holzmann, Stanislav Pantelyushin, Christian Wohn, Burkhard Becher, Cheolho Cheong, Stefan Haak, Björn E. Clausen, Sabina Onderwater, Julia L. Ober-Blöbaum, Sonja Zahner, Marius Kant |
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| Přispěvatelé: | University of Zurich, Clausen, Björn E, Immunology, Child and Adolescent Psychiatry / Psychology, Dermatology |
| Jazyk: | angličtina |
| Rok vydání: | 2013 |
| Předmět: |
Langerin
CD11c 610 Medicine & health Inflammation 10263 Institute of Experimental Immunology Interleukin-23 Mice 03 medical and health sciences 0302 clinical medicine Psoriasis medicine Interleukin 23 Animals Lectins C-Type 030304 developmental biology Mice Knockout 1000 Multidisciplinary 0303 health sciences Imiquimod Membrane Glycoproteins Multidisciplinary biology integumentary system hemic and immune systems Dendritic cell TLR7 Biological Sciences Acquired immune system medicine.disease 3. Good health Disease Models Animal Mannose-Binding Lectins Toll-Like Receptor 7 Langerhans Cells 030220 oncology & carcinogenesis Antigens Surface Myeloid Differentiation Factor 88 Immunology Aminoquinolines biology.protein 570 Life sciences medicine.symptom |
| Zdroj: | Proc. Natl. Acad. Sci. U.S.A. 110, 10723-10728 (2013) Proceedings of the National Academy of Sciences of the United States of America Europe PubMed Central Proceedings of the National Academy of Sciences of the U.S.A., 110(26), 10723-10728. National Academy of Sciences |
| ISSN: | 0027-8424 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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