The Journal of Allergy and Clinical Immunology
Volume 123, Issue 1 , Pages 59-66.e4, January 2009

IL-17 in atopic eczema: Linking allergen-specific adaptive and microbial-triggered innate immune response

  • Kilian Eyerich, MD

      Affiliations

    • Laboratory of Immunology, IDI-IRCCS, Rome, Italy
    • Corresponding Author InformationReprint requests: Kilian Eyerich, MD, Laboratory of Immunology, IDI-IRCCS, Via dei Monti di Creta 104, 00167 Rome, Italy.
    • These authors contributed equally to this work.
    • ,
  • Davide Pennino, PhD

      Affiliations

    • Laboratory of Immunology, IDI-IRCCS, Rome, Italy
    • These authors contributed equally to this work.
    • ,
  • Claudia Scarponi, PhD

      Affiliations

    • Laboratory of Immunology, IDI-IRCCS, Rome, Italy
    • ,
  • Stefanie Foerster, PhD,

      Affiliations

    • ZAUM–Center for Allergy and Environment, Division of Environmental Dermatology and Allergy Helmholtz Zentrum/TUM, Munich, Germany
    • ,
  • Francesca Nasorri, PhD

      Affiliations

    • Laboratory of Immunology, IDI-IRCCS, Rome, Italy
    • ,
  • Heidrun Behrendt, MD

      Affiliations

    • ZAUM–Center for Allergy and Environment, Division of Environmental Dermatology and Allergy Helmholtz Zentrum/TUM, Munich, Germany
    • ,
  • Johannes Ring, MD, PhD

      Affiliations

    • Department of Dermatology and Allergy, Technische Universität München, Munich, Germany
    • ,
  • Claudia Traidl-Hoffmann, MD

      Affiliations

    • ZAUM–Center for Allergy and Environment, Division of Environmental Dermatology and Allergy Helmholtz Zentrum/TUM, Munich, Germany
    • ,
  • Cristina Albanesi, PhD

      Affiliations

    • Laboratory of Immunology, IDI-IRCCS, Rome, Italy
    • ,
  • Andrea Cavani, MD, PhD

      Affiliations

    • Laboratory of Immunology, IDI-IRCCS, Rome, Italy

Received 2 July 2008; received in revised form 16 October 2008; accepted 20 October 2008. published online 04 December 2008.

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 β-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 TH2/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-γ, or both were efficiently induced. IL-17 secretion was not enhanced by IL-23, IL-1β, 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-γ, and IL-10 were marginally regulated. Induced IL-17 upregulated HBD-2 in human keratinocytes in vivo.

Conclusion

IL-17–capable T cells, in particular TH2/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.

Key words: Atopic eczema/dermatitis, TH17, IL-17, superantigen, defensin

Abbreviations used: AE, Atopic eczema, APC, Antigen-presenting cell, APT, Atopy patch test, DC, Dendritic cell, HBD-2, Human β-defensin 2, FITC, Fluorescein isothiocyanate, PE, Phycoerythrin, PMA, Phorbol 12-myristate 13-acetate, SEB, Staphylococcal enterotoxin B, TCR, T-cell receptor

 

 K. Eyerich was supported by a grant of the “Bayerische Forschungsstiftung” (BFS). This work was supported by a grant of the European Community (UE-LSHB-CT-2005-018681) and by the Italian minister of health.

 Disclosure of potential conflict of interest: The authors have declared that they have no conflict of interest.

PII: S0091-6749(08)01880-0

doi:10.1016/j.jaci.2008.10.031

The Journal of Allergy and Clinical Immunology
Volume 123, Issue 1 , Pages 59-66.e4, January 2009

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