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 Ly6Chi 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.
Highlights
Dendritic cells (DCs) have been implicated in the pathogenesis of psoriasis but the roles for specific DC subsets are not well defined
Dermal CD103 þ conventional DCs (cDCs) and CD11b þ cDCs are developmentally related to the lymphoid CD8a þ and CD8a À cDCs, respectively, which reside in secondary lymphoid tissues together with tissue migratory DCs1,2
DCs are abundant within psoriatic skin, and Plasmacytoid DCs (pDCs), resident cDCs and inflammatory DCs (iDCs) have all been proposed to be important for the initiation and/or maintenance of disease
Summary
Dendritic cells (DCs) have been implicated in the pathogenesis of psoriasis but the roles for specific DC subsets are not well defined. The critical DCs are TNF-producing and IL-1b-producing monocyte-derived DCs, including a population of inflammatory Langerhans cells. 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. Two major subsets of cDCs have been characterized in the mouse dermis, CD103 þ CD11b À (CD103 þ ) and CD103 À CD11b þ (CD11b þ ) cells, whereas the epidermis contains Langerhans cells (LCs)[1,2]. Fms-related tyrosine kinase ligand 3 (Flt3L) is indispensable for cDCs, but is not required for the development of monocyte-derived DCs (moDCs), macrophages and LCs1,2. Despite strong evidence implicating DCs in psoriasis, the contribution of specific DC subsets to disease pathogenesis remains undefined
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