Psoriasis pathophysiology: current concepts of pathogenesis (original) (raw)

Abstract

Psoriasis vulgaris is a common skin disorder characterised by focal formation of inflamed, raised plaques that constantly shed scales derived from excessive growth of skin epithelial cells. The disease is defined by a series of linked cellular changes in the skin: hyperplasia of epidermal keratinocytes, vascular hyperplasia and ectasia, and infiltration of T lymphocytes, neutrophils, and other types of leucocyte in affected skin. In a relatively short period, psoriasis vulgaris has been conceptualised as a T lymphocyte mediated autoimmune disease and new biological therapies that target T cells have just entered routine clinical practice. Similarly, rapid progress has been made towards dissecting cellular and molecular pathways of inflammation that contribute to disease pathogenesis. This short review presents current pathogenic concepts that have emerged from genetic, genomic, and cellular information obtained in basic studies and from clinical studies of selective immune targeting drugs.

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Figure 1.

Figure 1

The array of leucocyte subsets that appear in psoriasis vulgaris lesions. iDC, immature dendritic cell; NK-T, natural killer T (cells).

Figure 2.

Figure 2

Alternative pathways of leucocyte activation that converge to activate type 1 inflammatory genes which, in turn, regulate end stage inflammation in skin and the appearance of the psoriasis phenotype. BRL, Bonzo receptor ligand; DC, dendritic cell; ICAM, intercellular adhesion molecule; ITAC, interferon inducible T cell α chemoattractant; IL, interleukin; IFN, interferon; iNOS, inducible nitric oxide synthase; IP10, interferon inducible protein 10; IRF, interferon regulatory factor; ISF, interferon stimulated factor; LFA-1, leucocyte function associated antigen-1; MCP, monocyte chemoattractant protein; MIG, monokine induced by interferon γ; MIP, macrophage inflammatory protein; MxA, interferon induced cellular resistance mediator protein; NF, nuclear factor; NK, natural killer (cell); PARC, pulmonary and activation regulated chemokine; PNAd, peripheral node addressin; TNF tumour necrosis factor; SLC, secondary lymphoid tissue chemokine; STAT, signal transducer and activator of transcription; VCAM, vascular cell adhesion molecule; VEGF, vascular endothelial growth factor.

Selected References

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