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

Authors

  • L. W. J. van den Elsen,

    1. Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, the Netherlands
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  • L. A. P. M. Meulenbroek,

    1. Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, the Netherlands
    2. Department of Dermatology/Allergology, University Medical Centre Utrecht, Utrecht, the Netherlands
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  • B. C. A. M. van Esch,

    1. Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, the Netherlands
    2. Danone Research, Centre for Specialised Nutrition, Wageningen, the Netherlands
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  • G. A. Hofman,

    1. Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, the Netherlands
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  • L. Boon,

    1. Bioceros BV, Utrecht, the Netherlands
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  • J. Garssen,

    1. Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, the Netherlands
    2. Danone Research, Centre for Specialised Nutrition, Wageningen, the Netherlands
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  • L. E. M. Willemsen

    Corresponding author
    1. Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, the Netherlands
    • Correspondence

      Linette E. M. Willemsen, Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, P.O. Box 80082, 3508 TB, Utrecht, the Netherlands.

      Tel.: +31/30/20245763

      Fax: +31/30/2537900

      Email: L.E.M.Willemsen@uu.nl

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  • Edited by: Angela Haczku

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.

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