The Origin of Skin Dendritic Cell Network and Its Role in Psoriasis

Abstract

Dendritic cells (DCs) are heterogeneous groups of innate immune cells, which orchestrate immune responses by presenting antigens to cognate T cells and stimulating other types of immune cells. Although the term 'DCs' generally represent highly mixed subsets with functional heterogeneity, the classical definition of DCs usually denotes conventional DCs (cDCs). Skin contains a unique DC network mainly composed of embryo precursor-derived epidermal Langerhans cells (LCs) and bone marrow-derived dermal cDCs, which can be further classified into type 1 (cDC1) and type 2 (cDC2) subsets. Psoriasis is a chronic inflammatory skin disease, which is principally mediated by IL-23/IL-17 cytokine axis. In the psoriatic skins, DCs are prominent cellular sources for TNF-alpha and IL-23, and the use of blocking antibodies against TNF-alpha and IL-23 leads to a significant clinical improvement in psoriatic patients. Recent elegant human and mouse studies have shown that inflammation-induced inflammatory DCs, LCs, dermal cDC2, and monocyte-derived DCs are pivotal DC subsets in psoriatic inflammation. Thus, targeting specific pathogenic DC subsets would be a potential strategy for alleviating and preventing DC-derived IL-23-dependent psoriatic inflammation and other inflammatory dermatoses in the future.