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Author
I.J. Kosten
S.W. Spiekstra
T.D. de Gruijl
S. Gibbs
Year
2016
Title
MUTZ-3 Langerhans cell maturation and CXCL12 independent migration in reconstructed human gingiva
Journal
Altex-Alternatives To Animal Experimentation
Volume | Issue number
33 | 4
Pages (from-to)
423-434
Number of pages
12
Document type
Article
Faculty
Faculty of Dentistry (ACTA)
Abstract

Here we describe a reconstructed full thickness human oral mucosa (gingiva) equivalent with integrated Langerhans cells (GE-LC) and use it to compare LC activation and migration from oral versus skin epithelium. The physiologically representative models consist of differentiated reconstructed epithelium (keratinocytes and Langerhans-like cells derived from the MUTZ-3 cell line) on a fibroblast-populated collagen hydrogel, which serves as a lamina propria for gingiva and dermis for skin. Topical exposure of GE-LC and the skin equivalent (SE-LC) to subtoxic concentrations of the allergens cinnamaldehyde, resorcinol and nickel sulfate resulted in LC migration out of the epithelia. Neutralizing antibody to CXCL12 blocked allergen-induced LC migration in SE-LC but not in GE-LC. Also, gingival fibroblasts secreted very low amounts of CXCL12 compared to skin fibroblasts, even when stimulated with rhTNFα or rhIL-1α. Surprisingly, cinnamaldehyde exposure of GE-LC resulted in an increase in MUTZ-3 LC and CD83 mRNA in the hydrogel but did not result in an increase in CD1a+ cells in the collagen hydrogel (as was observed for SE-LC). These results indicate that in gingiva, upon allergen exposure, MUTZ-3 LC migrate in a CXCL12 independent manner from epithelium to lamina propria and in so doing mature by becoming CD1a- and increasing CD83+ mRNA. These physiologically relevant in vitro models, which not only are human but which also resemble specific tissues, may aid in the identification of factors regulating immune stimulation, which in turn will aid the development of therapeutic interventions for allergy and inflammation, anti-cancer vaccines as well as improving diagnostics for skin and oral allergy.

URL
go to publisher's site
Other links
Link to publication in Scopus
Language
English
Permalink
http://hdl.handle.net/11245.1/bc925aef-0341-4a21-96b6-b32b07aa3c2f
Downloads
  • altex_2016_4_423_434_Kosten11

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