Recent developments in the understanding of the pathogenesis of psoriasis

Abstract

Recent studies have provided new insights into the molecular mechanisms involved in the pathogenesis of psoriasis. Patients may inherit a predisposition to psoriasis, although the disease is expressed only after being triggered by certain environmental or antigenic factors. There is considerable genetic heterogeneity in psoriasis and several genetic loci associated with the occurrence of the disease have been identified. Although the underlying abnormality in psoriasis has not been definitively identified, recent evidence suggests that activated T lymphocytes play an important role in the pathogenesis of the disease. The activation of T lymphocytes can be mediated through antigen-presenting cells or through autoimmunity, and is influenced by cytokines. Recently developed animal models and in vitro studies of psoriasis have provided new evidence for the role of pathogenic lymphocytes in the initiation of the disease process. Further research will help to identify the susceptibility genes involved in psoriasis and provide a more complete understanding of the immunological basis of the disease. This should lead to the development of targeted therapies with improved efficacy and tolerability compared with some currently available treatments.

Tumour necrosis factor (TNF) in psoriatic arthritis: pathophysiology and treatment with TNF inhibitors

“…11 Activation of T lymphocytes, antigen presenting cells, and adhesion molecules through autoimmune mechanisms is believed to play a key, probably overlapping, role in the epidermal hyperproliferation of psoriasis. 12 The cytokines produced in response to immune activation are also critical contributors to disease pathogenesis. For example, proinflammatory cytokines such as TNF are found in high levels in the skin lesions and plasma of patients with psoriasis.…”

Serum lipid profile paraoxonase and arylesterase activities in psoriasis

“…1 There is some evidence regarding to abnormalities in the membrane lipid composition and/or features. Differences not only have been observed in plasma membranes but also in lymphocytes, polymorphonuclear leukocytes, and platelets of psoriatic patients.…”

Narrowband (312-nm) UV-B Suppresses Interferon γ and Interleukin (IL) 12 and Increases IL-4 Transcripts

“…2,3 Recent measures of ongoing cytokine synthesis in psoriatic lesions by reverse transcription-polymerase chain reaction (RT-PCR) techniques confirm the predominance of proinflammatory cytokine messenger RNAs (mRNAs) (IFN-␥, TNF-␣, and IL-8) and a paucity of suppressive cytokine mRNAs (IL-4 and IL-10). 4 In addition, IL-12 and its receptor are overexpressed in psoriatic lesions.…”

“…Hence, there is a proposed "type 1" inflammatory cascade in psoriasis: IL-12 induces IFN-␥ synthesis by T cells; in turn, IFN-␥ induces synthesis of many downstream genes and proteins that include T-cell-activating adhesion molecules (intracellular adhesion molecule 1, HLA-DR, and CD40), chemokines that increase trafficking of leukocytes into skin lesions (IL-8, macrophage IFN-␥ inducible gene, and inducible protein 10), and molecules that are directly inflammatory in tissue. 3,6 The type 1 inflammatory axis is clinically relevant in psoriasis because many new biologic therapies being tested in psoriasis target IL-12, IFN-␥, or downstream molecules regulated by IFN-␥.…”