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Eyerich, S. ; Wagener, J.* ; Wenzel, V. ; Scarponi, C.* ; Pennino, D. ; Albanesi, C.* ; Schaller, M.* ; Behrendt, H. ; Ring, J.* ; Schmidt-Weber, C.B. ; Cavani, A.* ; Mempel, M.* ; Traidl-Hoffmann, C. ; Eyerich, K.

IL-22 and TNF-α represent a key cytokine combination for epidermal integrity during infection with Candida albicans.

Eur. J. Immunol. 41, 1894-1901 (2011)
DOI PMC
Open Access Green as soon as Postprint is submitted to ZB.
T cells exercise their full impact on target cells through a combination of secreted cytokines. The recently described T helper cell subset Th22 is characterized by a combinatorial secretion of IL-22 and TNF-α. Here, we demonstrate that IL-22 increases the TNF-α-dependent induction and secretion of several immune-modulatory molecules such as initial complement factors C1r and C1s, antimicrobial peptides S100A7 and HBD-2 (human β defensin 2), and antimicrobial chemokines CXCL-9/-10/-11 in primary human keratinocytes. The synergism of IL-22 and TNF-α is transmitted intracellularly by MAP kinases and downstream by transcription factors of the AP-1 family. The induction of innate immunity is relevant in an in vitro infection model, where keratinocytes stimulated with Th22 supernatants or recombinant IL-22 plus TNF-α effectively inhibit the growth of Candida albicans and maintain survival of epithelia. Accordingly, the combinatorial stimulation of keratinocytes with IL-22 and TNF-α most efficiently conserves the integrity of the epidermal barrier in a three-dimensional skin infection model as compared with IFN-γ, IL-17, IL-22 or TNF-α alone. In summary, we demonstrate that IL-22 and TNF-α represent a potent, synergistic cytokine combination for cutaneous immunity.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Candida albicans; Epidermal integrity; IL-22; TNF-alpha
ISSN (print) / ISBN 0014-2980
e-ISSN 1521-4141
Journal European Journal of Immunology
Quellenangaben Volume: 41, Issue: 7, Pages: 1894-1901 Article Number: , Supplement: ,
Publisher Wiley
Publishing Place Hoboken
Reviewing status Peer reviewed
Institute(s) Institute of Lung Health and Immunity (LHI)
Institute of Epidemiology (EPI)