IL-22 and TNF-α represent a key cytokine combination for epidermal integrity during infection with Candida albicans.
Eur J Immunol
; 41(7): 1894-901, 2011 Jul.
Article
in En
| MEDLINE
| ID: mdl-21469124
ABSTRACT
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 ß 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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Candidiasis, Cutaneous
/
Interleukins
/
Tumor Necrosis Factor-alpha
/
Epidermis
Type of study:
Prognostic_studies
Limits:
Humans
/
Male
Language:
En
Journal:
Eur J Immunol
Year:
2011
Type:
Article
Affiliation country:
Germany