Figure 2.

Schematic diagram for the role of multiple cutaneous DCs in the pathogenesis of human psoriasis. Damaged keratinocytes release self-nucleotide, which forms LL-37-self-nucleotides complexes. The complexes directly stimulate plasmacytoid DCs to produce a large amount of type I interferons, which leads to maturation and activation of myeloid DCs. Activated DCs are able to produce IL-12 and IL-23 which primes and stimulates Th1 and Th17 cells, respectively. In the psoriatic lesions, there are cellular aggregates, which mainly comprise skin-infiltrating mDCs and Th1/Th17 cells. The formation of DC-T cell clusters is associated with CCL19/CCR7 and CCL20/CCR6 chemokine axis, which ultimately drives chronic T cell activation in situ. Effector cytokines mainly produced by T cells induce keratinocyte proliferation and aberrant differentiation, which are key characteristics of psoriasis. Cytokine-stimulated ketatinocytes also secrete chemokines, such as CCL20 and CXCL10, which efficiently recruit Th17 and Th1 cells into the lesions. Distinct inflammatory type of DCs, namely Tip-DCs arise in the psoriatic lesions and produce a large amount of pro-inflammatory cytokine to potentiate psoriatic inflammation. Recent studies have highlighted an autoimmune nature of psoriasis as psoriatic patients harbor self-reactive T cells clones against putative psoriasis autoantigens, including LL-37 and A disintegrin-like and metalloprotease domain containing thrombospondin type 1 motif-like 5 (ADAMTSL5).