IL-17 in atopic eczema: linking allergen-specific adaptive and microbial-triggered innate immune response.
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.
Eyerich
Kilian
K
Laboratory of Immunology, IDI-IRCCS, Rome, Italy. kilian.eyerich@gmx.de
Pennino
Davide
D
Scarponi
Claudia
C
Foerster
Stefanie
S
Nasorri
Francesca
F
Behrendt
Heidrun
H
Ring
Johannes
J
Traidl-Hoffmann
Claudia
C
Albanesi
Cristina
C
Cavani
Andrea
A
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
D016207:Cytokines; C106641:DEFB4A protein, human; D020381:Interleukin-17; D023083:beta-Defensins; D013755:Tetradecanoylphorbol Acetate