Pathogenesis and therapy of psoriasis

Abstract

Psoriasis is one of the most common human skin diseases and is considered to have key genetic underpinnings. It is characterized by excessive growth and aberrant differentiation of keratinocytes, but is fully reversible with appropriate therapy. The trigger of the keratinocyte response is thought to be activation of the cellular immune system, with T cells, dendritic cells and various immune-related cytokines and chemokines implicated in pathogenesis. The newest therapies for psoriasis target its immune components and may predict potential treatments for other inflammatory human diseases.

Psoriasis in humans is associated with down‐regulation of galectins in dendritic cells

“…Accordingly, several components of the pathways involved in T-cell activation are well-established targets in psoriasis antibody-based therapies, for example anti-TNF-alpha, anti-LFA-1, anti-LFA-3, and more recently anti-IL-12/IL-23 [14,27]. However, recent studies acknowledge the importance of anti-inflammatory signals that counterbalance the inflammatory response.…”

“…Experimental evidence indicates an involvement of Th1 and Th17 responses in the pathogenesis of psoriasis [14], a chronic inflammatory skin disease affecting 2 to 3% of the human population. Moreover, a recent study described a beneficial effect of gal-9 treatment in a model of IL-23-induced, psoriasis-like skin inflammation [15].…”

IL‐12, IL‐23, and IL‐27 enhance human β‐defensin‐2 production in human keratinocytes

“…In cutaneous infection or inflammatory diseases like psoriasis, hBD-2 production in epidermal keratinocytes is enhanced [7,32]. In these situations, APC such as DC, macrophages, and Langerhans cells are activated and these produce large amounts of IL-12, IL-23, and IL-27 in addition to the pro-inflammatory cytokine IL-1b [11,33]. Our present results thus suggest that IL-12, IL-23, and IL-27 may be the candidate stimuli for hBD-2 production in these situations and may promote antimicrobial defense or inflammation via hBD-2.…”

“…In cutaneous infection or inflammation, dermal or epidermal APC such as DC, Langerhans cells, and macrophages are increased and activated, and these abundantly produce IL-12, IL-23, and IL-27 [11][12][13]. In particular, IL-12 and IL-23 production is highly enhanced in psoriatic skin lesions [11].…”

“…In particular, IL-12 and IL-23 production is highly enhanced in psoriatic skin lesions [11]. It is thus plausible that these cytokines may act on epidermal keratinocytes and modulate the production of inflammatory or antimicrobial molecules.…”