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IL-10 Receptor or TGF-? Neutralization Abrogates the Protective Effect of a Specific Nondigestible Oligosaccharide Mixture in Cow-Milk-Allergic Mice.


ABSTRACT:

Background

Dietary nondigestible, short-chain galacto-, long-chain fructo-, and pectin-derived acidic oligosaccharides (GFAs) lower the effector response in cow-milk-allergic (CMA) mice; and forkhead box P3 (Foxp3)-positive regulatory T cells (Tregs) were shown to contribute to this.

Objective

The aim of this study was to assess the contribution of interleukin 10 (IL-10) and transforming growth factor ? (TGF-?) to the protective effect of the GFA diet in CMA mice.

Methods

Female C3H/HeOuJ mice, 3-4 wk old, were orally sensitized with cholera toxin (Sham) or whey and cholera toxin (Whey) 1 time/wk for 5 consecutive weeks and challenged with whey 1 wk later. The mice were fed a control or 1% GFA (9:2:1) (Whey+GFA) diet starting 2 wk before the first sensitization. In a second experiment, the mice were also injected with ?IL-10 receptor (?IL-10r), ?TGF-?, or isotype control antibodies 24 h before each sensitization. The acute allergic skin response, anaphylaxis score, whey-specific IgE, mucosal mast cell protease 1 (mMCP-1), and Treg frequency in the mesenteric lymph nodes (MLNs) and intestinal Foxp3, Il10, and Tgfb mRNA expression were determined.

Results

In Whey+GFA mice, intestinal Il10, Tgfb, or Foxp3 mRNA expression was 2-10 times higher (P < 0.05) and the MLN Treg frequency was 25% higher compared with Whey mice (P < 0.05). The acute allergic skin response was 50% lower in Whey+GFA mice compared with Whey mice (P < 0.01), and IL-10 receptor (IL-10r) or TGF-? neutralizing antibodies prevented this protective effect (P < 0.001). The Whey mice had higher serum mMCP-1 concentrations and whey-immunoglobulin E (-IgE) levels than Sham mice (P < 0.01), whereas these were not higher in Whey+GFA mice, and neutralizing antibodies partially interfered with these responses.

Conclusions

Dietary GFAs enhance the Treg frequency in the MLNs and mucosal IL-10 and TGF-? transcription while suppressing the allergic effector response. Neutralizing antibodies showed that the allergy-protective effect of the GFA diet was mediated by IL-10 and TGF-? in CMA mice.

SUBMITTER: Kerperien J 

PROVIDER: S-EPMC6074790 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature

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IL-10 Receptor or TGF-β Neutralization Abrogates the Protective Effect of a Specific Nondigestible Oligosaccharide Mixture in Cow-Milk-Allergic Mice.

Kerperien JoAnn J   Veening-Griffioen Désirée D   Wehkamp Tjalling T   van Esch Betty C A M BCAM   Hofman Gerard A GA   Cornelissen Paquita P   Boon Louis L   Jeurink Prescilla V PV   Garssen Johan J   Knippels Leon M J LMJ   Willemsen Linette E M LEM  

The Journal of nutrition 20180801 8


<h4>Background</h4>Dietary nondigestible, short-chain galacto-, long-chain fructo-, and pectin-derived acidic oligosaccharides (GFAs) lower the effector response in cow-milk-allergic (CMA) mice; and forkhead box P3 (Foxp3)-positive regulatory T cells (Tregs) were shown to contribute to this.<h4>Objective</h4>The aim of this study was to assess the contribution of interleukin 10 (IL-10) and transforming growth factor β (TGF-β) to the protective effect of the GFA diet in CMA mice.<h4>Methods</h4>F  ...[more]

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