Immunopathogenesis of psoriasis.
Psoriasis is a chronic skin disease that affects about 1.5% of the Caucasian population and is characterized by typical macroscopic and microscopic skin alterations. Psoriatic lesions are sharply demarcated, red and slightly raised lesions with silver-whitish scales. The microscopic alterations of psoriatic plaques include an infiltration of immune cells in the dermis and epidermis, a dilatation and an increase in the number of blood vessels in the upper dermis, and a massively thickened epidermis with atypical keratinocyte differentiation. It is considered a fact that the immune system plays an important role in the pathogenesis of psoriasis. Since the early 1990s, it has been assumed that T1 cells play the dominant role in the initiation and maintenance of psoriasis. However, the profound success of anti-tumor necrosis factor-alpha therapy, when compared with T-cell depletion therapies, should provoke us to critically re-evaluate the current hypothesis for psoriasis pathogenesis. Recently made discoveries regarding other T-cell populations such as Th17 and regulatory T cells, dendritic cells, macrophages, the keratinocyte signal transduction and novel cytokines including interleukin (IL)-22, IL-23 and IL-20, let us postulate that the pathogenesis of psoriasis consists of distinct subsequent stages, in each of them different cell types playing a dominant role. Our model helps to explain the varied effectiveness of the currently tested immune modulating therapies and may enable the prediction of the success of future therapies.
Sabat
Robert
R
Interdisciplinary Group of Molecular Immunopathology, Dermatology/Medical Immunology, University Hospital Charité, Berlin, Germany. robert.sabat@charite.de
Philipp
Sandra
S
Höflich
Conny
C
Kreutzer
Stefanie
S
Wallace
Elizabeth
E
Asadullah
Khusru
K
Volk
Hans-Dieter
HD
Sterry
Wolfram
W
Wolk
Kerstin
K
D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D002465:Cell Movement / Q000276:immunology; D006801:Humans; D015603:Keratinocytes / Q000276:immunology / Q000473:pathology; D007962:Leukocytes / Q000276:immunology; D018448:Models, Immunological; D011565:Psoriasis / Q000209:etiology / Q000276:immunology* / Q000473:pathology*; D012867:Skin / Q000276:immunology / Q000473:pathology; D016176:T-Lymphocyte Subsets / Q000276:immunology