CD25+ regulatory T cells transfer n-3 long chain polyunsaturated fatty acids-induced tolerance in mice allergic to cow's milk protein

Allergy. 2013 Dec;68(12):1562-70. doi: 10.1111/all.12300.

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.

Keywords: cow's milk allergy; fish oil; long‐chain n‐3 polyunsaturated fatty acids; regulatory T cell; tolerance.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adoptive Transfer
  • Animals
  • Body Temperature
  • Cattle
  • Diet
  • Disease Models, Animal
  • Fatty Acids, Omega-3 / immunology*
  • Fatty Acids, Omega-3 / pharmacology
  • Female
  • Fish Oils
  • Immune Tolerance* / drug effects
  • Immunoglobulin E / blood
  • Immunoglobulin E / immunology
  • Immunoglobulin G / blood
  • Immunoglobulin G / immunology
  • Interleukin-10 / biosynthesis
  • Interleukin-2 Receptor alpha Subunit / metabolism
  • Mice
  • Milk Hypersensitivity / immunology*
  • Milk Hypersensitivity / prevention & control*
  • Milk Proteins / immunology*
  • Spleen / cytology
  • T-Lymphocytes, Regulatory / immunology*
  • T-Lymphocytes, Regulatory / metabolism
  • Whey Proteins

Substances

  • Fatty Acids, Omega-3
  • Fish Oils
  • Immunoglobulin G
  • Interleukin-2 Receptor alpha Subunit
  • Milk Proteins
  • Whey Proteins
  • Interleukin-10
  • Immunoglobulin E