title: CD25+ regulatory T cells transfer n-3 long chain polyunsaturated fatty acids-induced tolerance in mice allergic to cow's milk protein.
abstract: BACKGROUND
  Recently, we have shown that dietary long-chain n-3 polyunsaturated fatty acids (n-3 LCPUFA) largely prevent allergic sensitization in a murine model for cow's milk allergy. The aim of this study was to assess the contribution of regulatory T cells (Treg) in the prevention of food allergy by n-3 LCPUFA.
  
  
  METHODS
  C3H/HeOuJ female donor mice were fed a control or fish oil diet before and during oral sensitization with cow's milk protein whey. Acute allergic skin response (ASR), anaphylaxis, body temperature, serum immunoglobulins, and mouse mast cell protease-1 (mmcp-1) were assessed. Splenocytes of sham- or whey-sensitized donor mice fed either control or fish oil diet were adoptively transferred to naïve recipient mice. Recipient mice received a whole splenocyte suspension, splenocytes ex vivo depleted of CD25+ cells, or MACS-isolated CD4+ CD25+ Treg. Recipient mice were sham- or whey-sensitized and fed control diet.
  
  
  RESULTS
  The ASR as well as whey-specific IgE and whey-specific IgG1 levels were reduced in whey-sensitized donor mice fed the fish oil diet as compared to the control diet. Splenocytes of control-diet-fed whey-sensitized donors transferred immunologic memory. By contrast, splenocytes of fish-oil-fed whey-sensitized - but not sham-sensitized - donors transferred tolerance to recipients as shown by a reduction in ASR and serum mmcp-1, and depletion of CD25+ Treg abrogated this. Transfer of CD25+ Treg confirmed the involvement of Treg in the suppression of allergic sensitization.
  
  
  CONCLUSIONS
  CD25+ Treg are crucial in whey allergy prevention by n-3 LCPUFA.
authors.affiliation: Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, the Netherlands.
authors.forename: L W J
authors.initials: LW
authors.lastname: van den Elsen
authors.forename: L A P M
authors.initials: LA
authors.lastname: Meulenbroek
authors.forename: B C A M
authors.initials: BC
authors.lastname: van Esch
authors.forename: G A
authors.initials: GA
authors.lastname: Hofman
authors.forename: L
authors.initials: L
authors.lastname: Boon
authors.forename: J
authors.initials: J
authors.lastname: Garssen
authors.forename: L E M
authors.initials: LE
authors.lastname: Willemsen
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D001831:Body Temperature; D002417:Cattle; D004032:Diet; D004195:Disease Models, Animal; D015525:Fatty Acids, Omega-3 / Q000276:immunology* / Q000494:pharmacology; D005260:Female; D005395:Fish Oils; D007108:Immune Tolerance / Q000187:drug effects; D007073:Immunoglobulin E / Q000097:blood / Q000276:immunology; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D016753:Interleukin-10 / Q000096:biosynthesis; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism; D051379:Mice; D016269:Milk Hypersensitivity / Q000276:immunology* / Q000517:prevention & control*; D008894:Milk Proteins / Q000276:immunology*; D013154:Spleen / Q000166:cytology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism; D000067816:Whey Proteins
chemical_list: D015525:Fatty Acids, Omega-3; D005395:Fish Oils; D007074:Immunoglobulin G; D053645:Interleukin-2 Receptor alpha Subunit; D008894:Milk Proteins; D000067816:Whey Proteins; D016753:Interleukin-10; D007073:Immunoglobulin E
keywords: cow's milk allergy; fish oil; long‐chain n‐3 polyunsaturated fatty acids; regulatory T cell; tolerance