title: IL-17 in atopic eczema: linking allergen-specific adaptive and microbial-triggered innate immune response.
abstract: BACKGROUND
  Patients with atopic eczema (AE) regularly experience colonization with Staphylococcus aureus that is directly correlated with the severity of eczema. Recent studies show that an impaired IL-17 immune response results in diseases associated with chronic skin infections.
  
  
  OBJECTIVE
  We sought to elucidate the effect of IL-17 on antimicrobial immune responses in AE skin.
  
  
  METHODS
  T cells infiltrating atopy patch test (APT) reactions were characterized for IL-17 secretion to varying stimuli. IL-17-dependent induction of the antimicrobial peptide human beta-defensin 2 (HBD-2) in keratinocytes was investigated.
  
  
  RESULTS
  Approximately 10% of APT-infiltrating T cells secreted IL-17 after phorbol 12-myristate 13-acetate (PMA)/ionomycin stimulation. Among these, 33% belonged to the newly characterized subtype T(H)2/IL-17. Despite the capacity to secrete IL-17, specific T-cell clones released only low amounts of IL-17 on cognate allergen stimulation, whereas IL-4, IFN-gamma, or both were efficiently induced. IL-17 secretion was not enhanced by IL-23, IL-1 beta, or IL-6 but was enhanced by the S aureus-derived superantigen staphylococcal enterotoxin B. Both healthy and AE keratinocytes upregulated HBD-2 in response to IL-17, but coexpressed IL-4/IL-13 partially inhibited this effect. In vivo, additional application of staphylococcal enterotoxin B induced IL-17 in APT reactions, whereas IL-4, IFN-gamma, and IL-10 were marginally regulated. Induced IL-17 upregulated HBD-2 in human keratinocytes in vivo.
  
  
  CONCLUSIONS
  IL-17-capable T cells, in particular T(H)2/IL-17 cells, infiltrate acute AE reactions. Although IL-17 secretion by specific T cells is tightly regulated, it can be triggered by bacteria-derived superantigens. The ineffective IL-17-dependent upregulation of HBD-2 in patients with AE is due to a partial inhibition by the type 2 microenvironment, which could partially explain why patients with AE do not clear S aureus.
authors.affiliation: Laboratory of Immunology, IDI-IRCCS, Rome, Italy. kilian.eyerich@gmx.de
authors.forename: Kilian
authors.initials: K
authors.lastname: Eyerich
authors.forename: Davide
authors.initials: D
authors.lastname: Pennino
authors.forename: Claudia
authors.initials: C
authors.lastname: Scarponi
authors.forename: Stefanie
authors.initials: S
authors.lastname: Foerster
authors.forename: Francesca
authors.initials: F
authors.lastname: Nasorri
authors.forename: Heidrun
authors.initials: H
authors.lastname: Behrendt
authors.forename: Johannes
authors.initials: J
authors.lastname: Ring
authors.forename: Claudia
authors.initials: C
authors.lastname: Traidl-Hoffmann
authors.forename: Cristina
authors.initials: C
authors.lastname: Albanesi
authors.forename: Andrea
authors.initials: A
authors.lastname: Cavani
mesh_terms: D016207:Cytokines / Q000276:immunology; D003876:Dermatitis, Atopic / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D005260:Female; D006801:Humans; D007113:Immunity, Innate; D020381:Interleukin-17 / Q000276:immunology*; D015603:Keratinocytes / Q000276:immunology* / Q000473:pathology; D008297:Male; D012867:Skin / Q000276:immunology / Q000382:microbiology; D012882:Skin Tests; D013207:Staphylococcal Skin Infections / Q000276:immunology* / Q000473:pathology; D013211:Staphylococcus aureus / Q000276:immunology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D018418:Th2 Cells / Q000276:immunology* / Q000473:pathology; D015854:Up-Regulation / Q000187:drug effects / Q000276:immunology; D023083:beta-Defensins / Q000276:immunology
chemical_list: D016207:Cytokines; C106641:DEFB4A protein, human; D020381:Interleukin-17; D023083:beta-Defensins; D013755:Tetradecanoylphorbol Acetate