Trends in Immunology
Volume 25, Issue 6, 1 June 2004, Pages 295-305
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Psoriasis vulgaris: cutaneous lymphoid tissue supports T-cell activation and ‘Type 1’ inflammatory gene expression

https://doi.org/10.1016/j.it.2004.03.006Get rights and content

Abstract

Psoriasis vulgaris is a common inflammatory skin disease that involves infiltration of leukocytes, activation of skin-resident cells and increased production of numerous cytokines, chemokines and inflammatory molecules. This Review presents an integrated view of disease pathogenesis, taking into account immune biology, broad-scale genomic characterization and the response of psoriasis to immune-targeted therapies. Recent studies suggest that activated dendritic cells (DCs) and T cells are central to its pathogenesis, causing ‘inflammation’ through a pathway of sequential interleukin-23 (IL-23) synthesis, interferon-γ (IFN-γ) production, activation of STAT1 (signal transducer and activator of transcription 1) and subsequent transcription of a broad series of IFN- and STAT-1-regulated genes. In situ expression of macrophage inflammatory protein-3β (MIP-3β; CCL19), secondary lymphoid tissue chemokine (SLC; CCL21) and other chemokines normally confined to formal lymphoid tissues, might help to sustain DC accumulation and overall activation of this inflammatory pathway.

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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