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  • Title: IL-31: a new link between T cells and pruritus in atopic skin inflammation.
    Author: Sonkoly E, Muller A, Lauerma AI, Pivarcsi A, Soto H, Kemeny L, Alenius H, Dieu-Nosjean MC, Meller S, Rieker J, Steinhoff M, Hoffmann TK, Ruzicka T, Zlotnik A, Homey B.
    Journal: J Allergy Clin Immunol; 2006 Feb; 117(2):411-7. PubMed ID: 16461142.
    Abstract:
    BACKGROUND: IL-31 is a novel T-cell-derived cytokine that induces severe pruritus and dermatitis in transgenic mice, and signals through a heterodimeric receptor composed of IL-31 receptor A and oncostatin M receptor. OBJECTIVE: To investigate the role of human IL-31 in pruritic and nonpruritic inflammatory skin diseases. METHODS: The expression of IL-31 was analyzed by quantitative real-time PCR in skin samples of healthy individuals and patients with chronic inflammatory skin diseases. Moreover, IL-31 expression was analyzed in nonlesional skin of atopic dermatitis patients after allergen or superantigen exposure, as well as in stimulated leukocytes. The tissue distribution of the IL-31 receptor heterodimer was investigated by DNA microarray analysis. RESULTS: IL-31 was significantly overexpressed in pruritic atopic compared with nonpruritic psoriatic skin inflammation. Highest IL-31 levels were detected in prurigo nodularis, one of the most pruritic forms of chronic skin inflammation. In vivo, staphylococcal superantigen rapidly induced IL-31 expression in atopic individuals. In vitro, staphylococcal enterotoxin B but not viruses or T(H)1 and T(H)2 cytokines induced IL-31 in leukocytes. In patients with atopic dermatitis, activated leukocytes expressed significantly higher IL-31 levels compared with control subjects. IL-31 receptor A showed most abundant expression in dorsal root ganglia representing the site where the cell bodies of cutaneous sensory neurons reside. CONCLUSION: Our findings provide a new link among staphylococcal colonization, subsequent T-cell recruitment/activation, and pruritus induction in patients with atopic dermatitis. Taken together, these findings show that IL-31 may represent a novel target for antipruritic drug development.
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