Current concepts in the pathogenesis of psoriasis

Abstract

Psoriasis is a multi-factorial skin disease with a complex pathogenesis. Various factors which have been suggested to play a key role in the pathogenesis are T cells, antigen presenting cells (APC's), keratinocytes, Langerhans' cells, macrophages, natural killer cells, an array of Th1 type cytokines, certain growth factors like vascular endothelial growth factor (VEGF), keratinocyte growth factor (KGF), and others. It has been hypothesized that the disease starts with the activation of T cell by an unknown antigen, which leads to secretion of an array of cytokines by activated T cells, inflammatory cells, and keratinocytes. The characteristic lesion of psoriasis is due to the hyper-proliferation of the keratinocyte. Activated Langerhans' cells migrate from skin to lymph nodes presenting the antigen to nodal naïve T cells (cells that have not been activated by antigen previously). The T cells activated by non-antigen-dependent mechanism may, however, become antigen-specific memory cells that react with a cross-reactive auto-antigen such as keratin (molecular mimicry). The genetic background of the disease may be suggested from the fact that concordance rate is 63-73% in monozygotic twins, as compared to 17-20% in dizygotic twins. Several disease susceptibility loci have been suggested as predisposing factors, PSORS1-PSORS9.

Keywords: Autoimmunity; pathogenesis; psoriasis.

Figure 1

The current hypothesis by which T cells get activated and how the release of various mediators leads to the hyperproliferation of the keratinocyte. (Modified from Mehlis and Gordon, Krueger37) (A) T cell binds to an Antigen-Presenting Cell, (B) T cell receptor recognizes the antigen presented on MHC of the APC in an antigen specific interaction, (C) Non-antigen specific cell-interaction. The stimulation of both TCR and CD28 pathways lead to transcription of IL-2, TNF-α, GM-CSF and IFN-Y, (D) T cell is rolling on the endothelium, (E) T cell surface proteins are activated, (F) T cell binds to the endothelium and diapedesis occurs, (G) Dermal Th1 cells release IFN-Y and other cytokines, which lead to increases expression of inflammatory and adhesion proteins on keratinocytes, (H) Keratinocytes proliferate; synthesize angiogenic cytokines / chemokines that cause leukocyte trafficking and increase leukocyte adhesion to the endothelial cells.