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SHR Neuro Cancer Cardio Lipid Metab Microb

Singh, TP; Zhang, HH; Borek, I; Wolf, P; Hedrick, MN; Singh, SP; Kelsall, BL; Clausen, BE; Farber, JM.
Monocyte-derived inflammatory Langerhans cells and dermal dendritic cells mediate psoriasis-like inflammation.
Nat Commun. 2016; 7(12):13581-13581 Doi: 10.1038/ncomms13581 [OPEN ACCESS]
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Co-authors Med Uni Graz: Borek Izabela Malgorzata; Wolf Peter
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Abstract:: Dendritic cells (DCs) have been implicated in the pathogenesis of psoriasis but the roles for specific DC subsets are not well defined. Here we show that DCs are required for psoriasis-like changes in mouse skin induced by the local injection of IL-23. However, Flt3L-dependent DCs and resident Langerhans cells are dispensable for the inflammation. In epidermis and dermis, the critical DCs are TNF-producing and IL-1β-producing monocyte-derived DCs, including a population of inflammatory Langerhans cells. Depleting Ly6C^hi blood monocytes reduces DC accumulation and the skin changes induced either by injecting IL-23 or by application of the TLR7 agonist imiquimod. Moreover, we find that IL-23-induced inflammation requires expression of CCR6 by DCs or their precursors, and that CCR6 mediates monocyte trafficking into inflamed skin. Collectively, our results imply that monocyte-derived cells are critical contributors to psoriasis through production of inflammatory cytokines that augment the activation of skin T cells.
Find related publications in this database (using NLM MeSH Indexing): Adjuvants, Immunologic - administration & dosage; Adjuvants, Immunologic - pharmacology; Aminoquinolines - administration & dosage; Aminoquinolines - pharmacology; Animals -; Dendritic Cells - physiology; Drug Eruptions -; Gene Expression Regulation - drug effects; Humans -; Imiquimod -; Inflammation - chemically induced; Interleukin-23 - administration & dosage; Interleukin-23 - pharmacology; Langerhans Cells - classification; Langerhans Cells - physiology; Major Histocompatibility Complex -; Membrane Proteins - genetics; Membrane Proteins - metabolism; Mice -; Mice, Knockout -; Monocytes - physiology; Psoriasis - pathology; Skin - cytology