Comparative phenotypic and functional analysis of migratory dendritic cell subsets from human oral mucosa and skin

Antigen exposure to oral mucosa is generally thought to lead to immune tolerance induction. However, very little is known about the subset composition and function of dendritic cells (DC) migrating from human oral mucosa. Here we show that migratory DC from healthy human gingival explants consist of...

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Vydáno v:PloS one Ročník 12; číslo 7; s. e0180333
Hlavní autoři: Kosten, Ilona Jennifer, van de Ven, Rieneke, Thon, Maria, Gibbs, Susan, de Gruijl, Tanja D.
Médium: Journal Article
Jazyk:angličtina
Vydáno: United States Public Library of Science 13.07.2017
Public Library of Science (PLoS)
Témata:
Analysis
Antigens
Antigens, CD1 - metabolism
Bacteria
Biology and Life Sciences
Cell Differentiation
Cell Movement
Chemokines
CXCR4 protein
Cytokines
Cytokines - metabolism
Dendritic cells
Dendritic Cells - cytology
Dendritic Cells - immunology
Dermatology
Differentiation (biology)
Explants
Frequency distribution
Functional analysis
Gingiva
Health aspects
Humans
Immunity
Immunization
Immunological tolerance
Inflammation
Langerhans Cells - cytology
Langerhans Cells - immunology
Lymphatic system
Lymphocytes
Lymphocytes T
Medicine and Health Sciences
Mouth Mucosa - cytology
Mouth Mucosa - metabolism
Mucosa
Mucous membrane
Oral mucosa
Phenotype
Receptors, CXCR4 - metabolism
Risk factors
Skin
Skin - cytology
Skin - metabolism
Steady state
T cell receptors
T-Lymphocytes - immunology
Netherlands
ISSN:1932-6203, 1932-6203
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Popis
Shrnutí:Antigen exposure to oral mucosa is generally thought to lead to immune tolerance induction. However, very little is known about the subset composition and function of dendritic cells (DC) migrating from human oral mucosa. Here we show that migratory DC from healthy human gingival explants consist of the same phenotypic subsets in the same frequency distribution as DC migrating from human skin. The gingival CD1a+ Langerhans cell and interstitial DC subsets lacked CXCR4 expression in contrast to their cutaneous counterparts, pointing to different migration mechanisms, consistent with previous observations in constructed skin and gingival equivalents. Remarkably, without any exogenous conditioning, gingival explants released higher levels of inflammatory cytokines than human skin explants, resulting in higher DC migration rates and a superior ability of migrated DC to prime allogeneic T cells and to induce type-1 effector T cell differentiation. From these observations we conclude that rather than an intrinsic ability to induce T cell tolerance, DC migrating from oral mucosa may have a propensity to induce effector T cell immunity and maintain a high state of alert against possible pathogenic intruders in the steady state. These findings may have implications for oral immunization strategies.
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Conceptualization: IJK RvdV MT SG TDdG.Formal analysis: IJK RvdV MT SG TDdG.Funding acquisition: SG TDdG.Investigation: IJK RvdV MT SG TDdG.Methodology: IJK RvdV MT SG TDdG.Project administration: IJK RvdV MT SG TDdG.Resources: IJK RvdV MT SG TDdG.Supervision: IJK RvdV SG TDdG.Validation: IJK RvdV MT SG TDdG.Visualization: IJK RvdV MT SG TDdG.Writing – original draft: IJK RvdV MT SG TDdG.Writing – review & editing: IJK RvdV MT SG TDdG.
Competing Interests: The authors have read the journal's policy and Susan Gibbs has the following competing interests: she is the co-founder of A-Skin BV which is a spin-off company (SME) of the VU University medical center. This does not alter our adherence to PLOS ONE policies on sharing data and materials. The other authors have declared that no conflicts of interest exist.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0180333