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

Eniko Sonkoly, Anja Muller, Antti I. Lauerma, Andor Pivarcsi, Hortensia Soto, Lajos Kemeny, Harri Alenius, Marie Caroline Dieu-Nosjean, Stephan Meller, Juliane Rieker, Martin Steinhoff, Thomas K. Hoffmann, Thomas Ruzicka, Albert Zlotnik, Bernhard Homey

Research output: Contribution to journalArticle

565 Citations (Scopus)

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 H1 and TH2 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.

Original languageEnglish
Pages (from-to)411-417
Number of pages7
JournalJournal of Allergy and Clinical Immunology
Volume117
Issue number2
DOIs
Publication statusPublished - Feb 1 2006

    Fingerprint

Keywords

  • Atopic dermatitis
  • Cytokines
  • IL-31
  • Pruritus
  • Superantigen
  • T cells

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Sonkoly, E., Muller, A., Lauerma, A. I., Pivarcsi, A., Soto, H., Kemeny, L., Alenius, H., Dieu-Nosjean, M. C., Meller, S., Rieker, J., Steinhoff, M., Hoffmann, T. K., Ruzicka, T., Zlotnik, A., & Homey, B. (2006). IL-31: A new link between T cells and pruritus in atopic skin inflammation. Journal of Allergy and Clinical Immunology, 117(2), 411-417. https://doi.org/10.1016/j.jaci.2005.10.033