IL-31: A new link between T cells and pruritus in atopic skin inflammation

• Published in: Journal of Allergy and Clinical Immunology Vol. 117; no. 2; pp. 411 - 417
• Main Authors: Sonkoly, Eniko, Muller, Anja, Lauerma, Antti I., Pivarcsi, Andor, Soto, Hortensia, Kemeny, Lajos, Alenius, Harri, Dieu-Nosjean, Marie-Caroline, Meller, Stephan, Rieker, Juliane, Steinhoff, Martin, Hoffmann, Thomas K., Ruzicka, Thomas, Zlotnik, Albert, Homey, Bernhard
• Format: Journal Article
• Language: English
• Published: New York, NY Mosby, Inc 01.02.2006; Elsevier; Elsevier Limited
• Subjects: Allergic diseases; Allergies; atopic dermatitis; Biological and medical sciences; Cell culture; Chemokines; Cytokines; Dermatitis; Dermatitis, Atopic - immunology; Dermatitis, Atopic - metabolism; Dermatitis, Atopic - physiopathology; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Ganglia, Spinal - metabolism; Gene expression; Humans; IL-31; Immunopathology; Interleukins - metabolism; Ligands; Lymphocyte Activation; Lymphocytes; Medical sciences; Prurigo - immunology; Prurigo - metabolism; pruritus; Pruritus - immunology; Pruritus - metabolism; Pruritus - physiopathology; Psoriasis; Psoriasis - immunology; Psoriasis - metabolism; Quality of life; Receptors, Interleukin - metabolism; Rodents; Skin; Skin allergic diseases. Stinging insect allergies; Staphylococcus aureus - immunology; Statistical analysis; Studies; superantigen; Superantigens - immunology; T cells; T-Lymphocytes - immunology; Up-Regulation; pruritus; SEB; atopic dermatitis; cytokines; TSST-1; T cells; superantigen; OSMR; IL-31RA; IL-31; Allergy; Immunopathology; Skin disease; Cytokine; Inflammation; Pruritus; Atopy; Immunology; Atopic dermatitis; Interleukin 31; T-Lymphocyte; Superantigen
• ISSN: 0091-6749; 1097-6825; 1097-6825; 1365-2567
• DOI: 10.1016/j.jaci.2005.10.033

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. To investigate the role of human IL-31 in pruritic and nonpruritic inflammatory skin diseases. 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. 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 H1 and T H2 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. 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.