Document Detail

IL-17 in atopic eczema: linking allergen-specific adaptive and microbial-triggered innate immune response.
MedLine Citation:
PMID:  19056110     Owner:  NLM     Status:  MEDLINE    
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. CONCLUSION: 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.
Kilian Eyerich; Davide Pennino; Claudia Scarponi; Stefanie Foerster; Francesca Nasorri; Heidrun Behrendt; Johannes Ring; Claudia Traidl-Hoffmann; Cristina Albanesi; Andrea Cavani
Publication Detail:
Type:  Journal Article; Multicenter Study; Research Support, Non-U.S. Gov't     Date:  2008-12-03
Journal Detail:
Title:  The Journal of allergy and clinical immunology     Volume:  123     ISSN:  1097-6825     ISO Abbreviation:  J. Allergy Clin. Immunol.     Publication Date:  2009 Jan 
Date Detail:
Created Date:  2009-01-09     Completed Date:  2009-01-27     Revised Date:  2010-09-17    
Medline Journal Info:
Nlm Unique ID:  1275002     Medline TA:  J Allergy Clin Immunol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  59-66.e4     Citation Subset:  AIM; IM    
Laboratory of Immunology, IDI-IRCCS, Rome, Italy.
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MeSH Terms
Cytokines / immunology
Dermatitis, Atopic / immunology*,  microbiology,  pathology
Immunity, Innate*
Interleukin-17 / immunology*
Keratinocytes / immunology*,  pathology
Skin / immunology,  microbiology
Skin Tests
Staphylococcal Skin Infections / immunology*,  pathology
Staphylococcus aureus / immunology*
Tetradecanoylphorbol Acetate / pharmacology
Th2 Cells / immunology*,  pathology
Up-Regulation / drug effects,  immunology
beta-Defensins / immunology
Reg. No./Substance:
0/Cytokines; 0/DEFB4A protein, human; 0/Interleukin-17; 0/beta-Defensins; 16561-29-8/Tetradecanoylphorbol Acetate

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