title: MUTZ-3 Langerhans cell maturation and CXCL12 independent migration in reconstructed human gingiva.
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 sub-toxic concentrations of the allergens cinnamaldehyde, resorcinol and nickel sulphate, 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 doing so mature become CD1a- and increase 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.
authors.affiliation: Department of Dermatology, VU University Medical Center, Amsterdam, the Netherlands.
authors.forename: Ilona J
authors.initials: IJ
authors.lastname: Kosten
authors.affiliation: Department of Dermatology, VU University Medical Center, Amsterdam, the Netherlands.
authors.forename: Sander W
authors.initials: SW
authors.lastname: Spiekstra
authors.affiliation: Department of Medical Oncology, VU University Medical Center, Amsterdam, the Netherlands.
authors.forename: Tanja D
authors.initials: TD
authors.lastname: de Gruijl
authors.affiliation: Department of Dermatology, VU University Medical Center, Amsterdam, the Netherlands.|Department of Oral Cell Biology, Academic Center for Dentistry (ACTA), University of Amsterdam and VU University, Amsterdam, the Netherlands.
authors.forename: Susan
authors.initials: S
authors.lastname: Gibbs
mesh_terms: D000485:Allergens; D000906:Antibodies; D002454:Cell Differentiation; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects*; D054377:Chemokine CXCL12 / Q000235:genetics / Q000378:metabolism*; D002633:Chemotaxis; D005786:Gene Expression Regulation; D005881:Gingiva / Q000502:physiology*; D006801:Humans; D007801:Langerhans Cells / Q000502:physiology*; D023822:Tissue Engineering / Q000379:methods*
chemical_list: D000485:Allergens; D000906:Antibodies; D054377:Chemokine CXCL12
keywords: allergen; dendritic cell; gingiva equivalent; in vitro; skin equivalent