Technical Advance: Langerhans cells derived from a human cell line in a full-thickness skin equivalent undergo allergen-induced maturation and migration

Journal of Leukocyte Biology

Sander W. Spiekstra¹  Krista Ouwehand¹  Susan Gibbs¹  Rik J. Scheper¹  Taco Waaijman¹  Tanja D. de Gruijl and¹ 

[1] Departments of Dermatology,  Pathology, and Medical Oncology, VU University Medical Centre, Amsterdam, The Netherlands

关键词: MUTZ-3;    in vitro;    keratinocyte;    fibroblast;    sensitization;    vaccination strategies;   

DOI  :  10.1189/jlb.0610374

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

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 NiSO4 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-1β 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.

【 授权许可】

Unknown