Epidermal HLA-DR and the enhancement of cutaneous reactivity to superantigenic toxins in psoriasis
| Autor: | David A. Norris, Qutayba Hamid, Evan R. Farmer, Patrick M. Schlievert, Christine Kuhn, Donald Y.M. Leung, Jeffrey B. Travers, Ralph Giorno |
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| Rok vydání: | 1999 |
| Předmět: |
Enterotoxin type B
integumentary system Toxic shock syndrome chemical and pharmacologic phenomena General Medicine Atopic dermatitis Enterotoxin Biology medicine.disease medicine.disease_cause body regions medicine.anatomical_structure Staphylococcus aureus Psoriasis Immunology medicine Superantigen Keratinocyte |
| Zdroj: | Journal of Clinical Investigation. 104:1181-1189 |
| ISSN: | 0021-9738 |
| DOI: | 10.1172/jci6835 |
| Popis: | Streptococcal and staphylococcal superantigens (SAg's) have been implicated in the pathogenesis of inflammatory skin diseases, but the mechanisms by which these toxins act are unknown. The present study assessed the ability of nanogram quantities of topically applied purified toxic shock syndrome toxin-1 (TSST-1), staphylococcal enterotoxin type B, and streptococcal pyrogenic enterotoxin types A and C to induce inflammatory reactions in clinically uninvolved skin of normal controls and subjects with psoriasis, atopic dermatitis, and lichen planus. These SAg's triggered a significantly greater inflammatory skin response in psoriatics than in normal control subjects or in subjects with atopic dermatitis or lichen planus. Surprisingly, skin biopsies did not exhibit the T-cell receptor Vbeta stimulatory properties predicted for SAg-induced skin reactions. By 6 hours after patch testing with SAg's, TNF-alpha mRNA had increased in the epidermis (but not the dermis) in biopsies from psoriatics, compared with controls. Immunohistochemical studies revealed significantly higher HLA-DR expression in keratinocytes from psoriatics than from controls. However, a mutant TSST-1 protein that fails to bind HLA-DR did not elicit an inflammatory skin reaction. These results indicate that keratinocyte expression of HLA-DR enhances inflammatory skin responses to SAg's. They may also account for previous studies failing to demonstrate selective expansion of T-cell receptor Vbetas in psoriatics colonized with SAg-producing Staphylococcus aureus, and they identify a novel T cell-independent mechanism by which SAg's contribute to the pathogenesis of inflammatory skin diseases. |
| Databáze: | OpenAIRE |
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