Journal
JOURNAL OF LEUKOCYTE BIOLOGY
Volume 90, Issue 5, Pages 1027-1033Publisher
FEDERATION AMER SOC EXP BIOL
DOI: 10.1189/jlb.0610374
Keywords
MUTZ-3; in vitro; keratinocyte; fibroblast; sensitization; vaccination strategies
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Funding
- VUmc Institute for Cancer and Immunology (V-ICI), Amsterdam
- European Commission [LSHB-CT-2005-018681]
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In this report, the construction of a functional, immunocompetent, full-thickness skin equivalent (SE) is described, consisting of an epidermal compartment containing keratinocytes, melanocytes, and human LCs derived from the MUTZ-3 cell line (MUTZ-LC) and a fibroblast-populated dermal compartment. The CD1a(+)Langerin(+)HLA-DR(+) MUTZ-LCs populate the entire epidermis at a similar density to that found in native skin. Exposure of the SE to subtoxic concentrations of the allergens NiSO(4) and resorcinol resulted in LC migration out of the epidermis toward the fibroblast-populated dermal compartment. A significant dose-dependent up-regulation of the DC maturation-related CCR7 and IL-1 beta transcripts and of CD83 at the protein level upon epidermal exposure to both allergens was observed, indicative of maturation and migration of the epidermally incorporated LC. We have thus successfully developed a reproducible and functional full-thickness SE model containing epidermal MUTZ-LC. This model offers an alternative to animal testing for identifying potential chemical sensitizers and for skin-based vaccination strategies and provides a unique research tool to study human LC biology in situ under controlled in vitro conditions. J. Leukoc. Biol. 90: 1027-1033; 2011.
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