Phl p 5 resorption in human oral mucosa leads to dose-dependent and time-dependent allergen binding by oral mucosal Langerhans cells, attenuates their maturation, and enhances their migratory and TGF-beta1 and IL-10-producing properties.
BACKGROUND
Sublingual immunotherapy (SLIT) is safe and effective as treatment of allergic rhinitis and mild asthma. Oral mucosal Langerhans cells (oLCs) play a central role. However, little is known about allergen binding by oLCs during mucosal allergen resorption and its impact on oLC functions.


OBJECTIVE
Binding of Phl p 5 to oLCs was studied in a standardized ex vivo model to investigate mechanisms important for SLIT.


METHODS
Human oral mucosal biopsies were incubated with the grass pollen allergen Phl p 5. Migration, binding of Phl p 5, phenotype and cytokine production, and T-cell priming of Phl p 5-binding oLCs were analyzed.


RESULTS
Significant uptake required more than 5 minutes, and dose-dependent binding of Phl p 5 to oLCs was saturated at 100 microg/mL Phl p 5. Furthermore, Phl p 5 significantly increased the migratory capacity of oLCs but attenuated their maturation and strongly promoted the release of TGF-beta1 and IL-10 by oLCs themselves as well as by cocultured T cells.


CONCLUSIONS
Oral mucosal Langerhans cells bind Phlp5 in a dose-dependent and time-dependent manner, leading to an increased production of tolerogenic cytokines and an enhanced migratory capacity but decelerated maturation of oLCs.
Allam
Jean-Pierre
JP
Department of Dermatology and Allergy, University of Bonn, Bonn, Germany.
Würtzen
Peter A
PA
Reinartz
Markus
M
Winter
Jochen
J
Vrtala
Susanne
S
Chen
Kuan-Wei
KW
Valenta
Rudolf
R
Wenghoefer
Matthias
M
Appel
Thorsten
T
Gros
Eva
E
Niederhagen
Bernd
B
Bieber
Thomas
T
Lund
Kaare
K
Novak
Natalija
N
D000286:Administration, Sublingual; D000328:Adult; D000485:Allergens / Q000276:immunology; D001249:Asthma / Q000188:drug therapy* / Q000276:immunology; D002465:Cell Movement; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007167:Immunotherapy; D016753:Interleukin-10 / Q000276:immunology*; D007801:Langerhans Cells / Q000276:immunology*; D008297:Male; D008954:Models, Biological; D009061:Mouth Mucosa / Q000378:metabolism*; D010940:Plant Proteins / Q000276:immunology*; D011485:Protein Binding; D012220:Rhinitis / Q000188:drug therapy* / Q000276:immunology; D013997:Time Factors; D053773:Transforming Growth Factor beta1 / Q000276:immunology*; D015854:Up-Regulation
D000485:Allergens; C076049:Phl p V protein, Phleum pratense; D010940:Plant Proteins; D053773:Transforming Growth Factor beta1; D016753:Interleukin-10