Expert Reviews in Molecular Medicine

Review Article

Molecular pathophysiology of psoriasis and molecular targets of antipsoriatic therapy

Emőke Rácza1 c1 and Errol P. Prensa1

a1 Department of Dermatology and Department of Immunology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands.

Abstract

Psoriasis is a chronic inflammatory skin disease characterised by elevated red scaly plaques on specific body sites. Histologically, the plaques are defined by epidermal hyperplasia, epidermal and dermal infiltration by leukocytes, and changes in the dermal microvasculature. Differentiation and activation are disturbed in lesional psoriatic keratinocytes, and the pool of proliferating keratinocytes is increased, which is accompanied by enhanced production of proinflammatory cytokines, adhesion molecules and antimicrobial peptides. These changes in psoriatic keratinocytes are caused by altered expression of genes associated with epidermal differentiation, and by activation of signalling pathways involving signal transducer and activator of transcription 3 (STAT3), type I interferon (IFN) and mitogen-activated protein kinase (MAPK). The number of T cells, and myeloid and plasmacytoid dendritic cells (DCs) is markedly increased in psoriatic lesions. Myeloid DCs produce interleukin (IL)-23, tumour necrosis factor (TNF)-α and inducible nitric oxide synthase (iNOS), which are crucial cytokines in the pathogenesis of psoriasis. IL-23 stimulates the secretion of IL-22 by T helper 17 cells, and IL-22 induces epidermal hyperplasia. The crosstalk between keratinocytes and leukocytes via their proinflammatory cytokines creates the vicious circle of chronic skin inflammation seen in psoriasis. This suggests that optimal treatment of psoriasis needs to target pathogenic pathways in both leukocytes and keratinocytes.

Correspondence

c1 Corresponding author: Emőke Rácz, Erasmus MC, University Medical Center, Department of Immunology/Dermatology, P.O. Box 2040, 3000 CA Rotterdam, The Netherlands. Tel: +3110 7043430; Fax: +3110 7044731; E-mail: e.racz@erasmusmc.nl