title: The role of intestinal dendritic cells subsets in the establishment of food allergy.
abstract: BACKGROUND
  Food allergy affects approximately 6% of children and is the leading cause of hospitalization for anaphylactic reactions in westernized countries. Crucial in the establishment of allergy is the activation of dendritic cells (DC) leading to T helper 2-mediated responses.
  
  
  OBJECTIVE
  We, therefore, investigated whether changes in DC subsets precede the establishment of food allergy, and which DC subsets have functional relevance during allergic sensitization in a mouse model.
  
  
  METHODS
  Changes in DC populations in the intestine were analysed after exposure to cholera toxin alone and in combination with peanut extract (PE) as an allergen. To study the functional role of DC subsets in relation to food allergy, we used expansion of DC in vivo by treatment with Flt3L.
  
  
  RESULTS
  Sensitization to PE in this mouse model was accompanied by a shift in DC subsets in intestinal tissues towards more CD11b(+) DC and less CD103(+) DC. No significant changes in the plasmacytoid DC (pDC) numbers were observed. Flt3L treatment, resulting in the expansion of all DC subtypes, inhibited allergic manifestations in our model, including Th2 cytokine production, PE-specific IgE and PE-induced mast cell degranulation. pDC depletion reversed Flt3L-induced inhibition of IgE responses and mast cell degranulation. conclusions and clinical relevance: The establishment of food allergy is accompanied by profound changes in DC subsets in the intestine towards more inflammatory CD11b(+) DC. In addition, expansion of DC numbers by Flt3L, in particular pDC, inhibits the establishment of allergic manifestations in the intestine. These findings are of relevance for understanding the role of DC subsets early during the process of allergic sensitization, and may lead to new therapeutic or prophylactic opportunities to prevent food allergy.
authors.affiliation: Institute for Risk Assessment Sciences, Division of Toxicology, Immunotoxicology group, Utrecht University, Utrecht, The Netherlands. j.j.smit@uu.nl
authors.forename: J J
authors.initials: JJ
authors.lastname: Smit
authors.forename: M
authors.initials: M
authors.lastname: Bol-Schoenmakers
authors.forename: I
authors.initials: I
authors.lastname: Hassing
authors.forename: D
authors.initials: D
authors.lastname: Fiechter
authors.forename: L
authors.initials: L
authors.lastname: Boon
authors.forename: R
authors.initials: R
authors.lastname: Bleumink
authors.forename: R H H
authors.initials: RH
authors.lastname: Pieters
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000818:Animals; D015703:Antigens, CD / Q000276:immunology; D010367:Arachis / Q000737:chemistry*; D039481:CD11b Antigen / Q000276:immunology; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism*; D004195:Disease Models, Animal; D005260:Female; D005512:Food Hypersensitivity / Q000276:immunology* / Q000378:metabolism*; D039001:Integrin alpha Chains / Q000276:immunology; D007422:Intestines / Q000166:cytology* / Q000187:drug effects / Q000276:immunology*; D008198:Lymph Nodes / Q000166:cytology; D008565:Membrane Proteins / Q000494:pharmacology; D051379:Mice; D008809:Mice, Inbred C3H; D010936:Plant Extracts / Q000276:immunology*; D013047:Specific Pathogen-Free Organisms
chemical_list: D000276:Adjuvants, Immunologic; D015703:Antigens, CD; D039481:CD11b Antigen; D039001:Integrin alpha Chains; D008565:Membrane Proteins; D010936:Plant Extracts; C091367:alpha E integrins; C084881:flt3 ligand protein