Food allergies have become a major healthcare concern, hence preventive efforts to ensure oral tolerance induction to newly introduced antigens are particularly relevant. Given that transforming growth factor-β (TGF-β) plays a key role in immune tolerance, we tested whether an infant formula enriched with TGF-β would improve oral tolerance induction. A partially hydrolyzed whey protein-based formula was enriched with cow’s-milk-derived TGF-β (TGF-β-enriched formula) by adding a specific whey protein isolate (WPI). The manufacturing process was optimized to achieve a concentration of TGF-β within the range of human breast milk concentrations. Protection from allergic sensitization and immune response was assessed in a mouse model. Adult mice received the TGF-β-enriched formula, a control non-enriched formula, or water ad libitum for 13 days before sensitization and suboptimal tolerization to ovalbumin (OVA). When compared to non-tolerized mice, suboptimally-tolerized mice supplemented with the TGF-β-enriched formula showed significantly lower levels of total immunoglobulin-E (IgE) and OVA-specific (IgG1). Mouse mast-cell protease-1 (mMCP-1) and cytokine levels were also significantly decreased in suboptimally-tolerized mice fed the TGF-β-enriched formula. In conclusion, oral supplementation with cow’s-milk-derived TGF-β decreased allergic responses to newly introduced allergens and thus reduced the risk of developing food allergy.
Functional Transforming Growth Factor-β Receptor Type II Expression by CD4+ T Cells in Peyer's Patches Is Essential for Oral Tolerance Induction