title: 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.
abstract: 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.
authors.affiliation: Department of Dermatology and Allergy, University of Bonn, Bonn, Germany.
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Allam
authors.forename: Peter A
authors.initials: PA
authors.lastname: Würtzen
authors.forename: Markus
authors.initials: M
authors.lastname: Reinartz
authors.forename: Jochen
authors.initials: J
authors.lastname: Winter
authors.forename: Susanne
authors.initials: S
authors.lastname: Vrtala
authors.forename: Kuan-Wei
authors.initials: KW
authors.lastname: Chen
authors.forename: Rudolf
authors.initials: R
authors.lastname: Valenta
authors.forename: Matthias
authors.initials: M
authors.lastname: Wenghoefer
authors.forename: Thorsten
authors.initials: T
authors.lastname: Appel
authors.forename: Eva
authors.initials: E
authors.lastname: Gros
authors.forename: Bernd
authors.initials: B
authors.lastname: Niederhagen
authors.forename: Thomas
authors.initials: T
authors.lastname: Bieber
authors.forename: Kaare
authors.initials: K
authors.lastname: Lund
authors.forename: Natalija
authors.initials: N
authors.lastname: Novak
mesh_terms: 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
chemical_list: D000485:Allergens; C076049:Phl p V protein, Phleum pratense; D010940:Plant Proteins; D053773:Transforming Growth Factor beta1; D016753:Interleukin-10