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

Abstract

BackgroundDietary 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.ObjectiveThe 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.MethodsFemale 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 αIL-10 receptor (αIL-10r), αTGF-β, 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.ResultsIn 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-β 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.ConclusionsDietary GFAs enhance the Treg frequency in the MLNs and mucosal IL-10 and TGF-β 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-β in CMA mice.

The Dietary Fiber Pectin: Health Benefits and Potential for the Treatment of Allergies by Modulation of Gut Microbiota

“…The different POS can include galacturonic acid (GalA), rhamnose (Rha), arabinose (Ara), and galactose (Gal) [52]. GFAs, consisting of pAOS, have shown to lower immune responses in cow-milk-allergic (CMA) mice, to enhance regulatory T cell (T reg ) frequencies, and to induce mucosal IL-10 and TGF-β transcription while suppressing the allergic effector response [53]. Both animal studies and human clinical trials showed that dietary intervention with these dietary oligosaccharides early in life could lead to the prevention of atopic dermatitis, food allergy, and allergic asthma [10,37,54,55].…”

Immunomodulation by Human Milk Oligosaccharides: The Potential Role in Prevention of Allergic Diseases

“…In a murine model for hen's egg allergy, 2'FL or 6'SL were found to reduce allergy symptoms in association with the induction of IL-10 + T reg cells (39). Prebiotic mixtures, such as scGOS and lcFOS, have been studied more extensively for immunomodulatory effects in vivo, showing promising results with regards to preventing allergic diseases, such allergic asthma and food allergy and these effects also link to the induction of T reg responses (134)(135)(136)(137). This implies a need for additional in vivo studies to gain insight in the properties of (single) HMOS to modulate gut maturation and the development of the mucosal immune system.…”

Hypoallergenic infant formula lacks transforming growth factor beta activity and has a lower anti-inflammatory activity than regular infant formula

“…Cow milk or the recombinant growth factor was shown to increase plasma TGF-β concentrations (Ando et al, 2007;Ozawa et al, 2009). Additionally, the allergy-protective effect of dietary acidic oligosaccharides is mediated by TGF-β in mice with cow milk allergy (Kerperien et al, 2018). Cow milk had significant beneficial effects on skin wound healing in a preclinical model (Hemmati et al, 2018).…”