title: IL-31: a new link between T cells and pruritus in atopic skin inflammation.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Dermatology, Heinrich-Heine-University, Düsseldorf, Germany.
authors.forename: Eniko
authors.initials: E
authors.lastname: Sonkoly
authors.forename: Anja
authors.initials: A
authors.lastname: Muller
authors.forename: Antti I
authors.initials: AI
authors.lastname: Lauerma
authors.forename: Andor
authors.initials: A
authors.lastname: Pivarcsi
authors.forename: Hortensia
authors.initials: H
authors.lastname: Soto
authors.forename: Lajos
authors.initials: L
authors.lastname: Kemeny
authors.forename: Harri
authors.initials: H
authors.lastname: Alenius
authors.forename: Marie-Caroline
authors.initials: MC
authors.lastname: Dieu-Nosjean
authors.forename: Stephan
authors.initials: S
authors.lastname: Meller
authors.forename: Juliane
authors.initials: J
authors.lastname: Rieker
authors.forename: Martin
authors.initials: M
authors.lastname: Steinhoff
authors.forename: Thomas K
authors.initials: TK
authors.lastname: Hoffmann
authors.forename: Thomas
authors.initials: T
authors.lastname: Ruzicka
authors.forename: Albert
authors.initials: A
authors.lastname: Zlotnik
authors.forename: Bernhard
authors.initials: B
authors.lastname: Homey
mesh_terms: D003876:Dermatitis, Atopic / Q000276:immunology* / Q000378:metabolism / Q000503:physiopathology; D005727:Ganglia, Spinal / Q000378:metabolism; D006801:Humans; D007378:Interleukins / Q000378:metabolism*; D008213:Lymphocyte Activation; D011536:Prurigo / Q000276:immunology / Q000378:metabolism; D011537:Pruritus / Q000276:immunology* / Q000378:metabolism / Q000503:physiopathology; D011565:Psoriasis / Q000276:immunology / Q000378:metabolism; D018123:Receptors, Interleukin / Q000378:metabolism; D013211:Staphylococcus aureus / Q000276:immunology; D018089:Superantigens / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D015854:Up-Regulation
chemical_list: C502187:IL31 protein, human; C502188:IL31RA protein, human; D007378:Interleukins; D018123:Receptors, Interleukin; D018089:Superantigens