Trends in Immunology
Psoriasis vulgaris: cutaneous lymphoid tissue supports T-cell activation and ‘Type 1’ inflammatory gene expression
Section snippets
Key cellular features of psoriasis plaques
What is psoriasis vulgaris? The clinical appearance of the psoriasis lesion is a red, raised, scaly plaque, which can be several centimeters in diameter. Usually, the skin is covered with many individual lesions, separated by normal-appearing skin, however, in extreme cases, virtually all of the skin surface can be affected [1]. Psoriasis vulgaris is defined by a combination of large-sized lesions (>1 cm in diameter) and a characteristic histopathology. Histological features include (i) marked
Cellular events in the formation of a psoriasis plaque
There are progressive steps in the formation of a chronic plaque (Figure 2). On the basis of finding clonal populations of T cells in skin lesions 21, 22, it is hypothesized that pathogenic T cells are reactive to an as yet unidentified cutaneous antigen and that the process of generating skin-homing effector T-cell clones is initially the same as a normal cellular immune response. Hence, it seems probable that disease-mediating cells would initially be formed in skin-draining lymph nodes and
From cellular infiltrates to a molecular pathway of pathogenesis
The best insights into pathogenic inflammation at a molecular level come from medium- and large-scale genomic characterization of psoriasis lesions, with due consideration of therapeutic effects on cellular infiltrates and of gene expression changes during therapy-induced disease resolution (pharmacogenomics). This process began with quantitative studies of inflammatory gene sets using real-time RT-PCR 24, 26, and it has been extended to study of thousands of human genes on different series of
Genomic studies identify unexpected expression of chemokines with ability to organize lymphoid tissue in psoriasis plaques
Although the persistence of psoriasis skin lesions might be due to chronic presence of an (auto)antigen in the skin, the possibility exists that cellular inflammation could be sustained by other types of (innate) immune reactions or non-conventional antigen triggers (Box 3). Another factor in this equation is the rather curious clinical observation that chronic T-cell infiltration of skin lesions, even in severe cases, is rarely accompanied by significant lymphadenopathy. This observation,
Acknowledgements
Supported by NIH grants R01-AR049049, AI149572, AI49832, and M01-RR00102.
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