Immunopathogenesis of psoriasis.
Psoriasis is characterized by sustained T cell activation by antigen-presenting cells (APCs) in the lesions, and by a deviation of T cell differentiation to type 1 helper T and type 1 cytotoxic T cells, although no specific antigens have yet been determined. These characteristics are at least promoted by decreased IL-10 expression and the increased IL-12 expression observed in both the skin and stimulated peripheral blood mononuclear cells of psoriatic patients. Some of the cytokines produced by activated T cells are suspected to stimulate the proliferation of psoriatic keratinocytes. Among them, interferon-gamma is the most likely candidate, although interferon-gamma does not promote the growth of normal keratinocytes. In addition to the abnormal proliferation, psoriatic keratinocytes show abnormal differentiation and resistance to apoptosis. So far, however, it is still unknown whether these phenotypic and functional characteristics of psoriatic keratinocytes are only the consequences of the stimulation by activated T cells or are at least based on an inherent susceptibility. Recently, it has become clear that chemokines derived from activated keratinocytes or endothelial cells play a crucial role in recruiting T cells in the skin and inducing the neutrophilic infiltration that leads to the formation of subcorneal pustules (Munro's microabscess). Finally, recent developments in the detection and analysis of gene expression have revealed the molecules responsible for these steps. Some of them have become target molecules for the treatment of psoriasis. And indeed, it has become possible now to treat patients with new, innovative drugs.
Ozawa
Maki
M
Department of Dermatology, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aobaku, Sendai, 980-8574, Japan.
Aiba
Setsuya
S
D000818:Animals; D002454:Cell Differentiation / Q000276:immunology; D002455:Cell Division / Q000276:immunology; D002465:Cell Movement / Q000276:immunology; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D006801:Humans; D011565:Psoriasis / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*
D016207:Cytokines