Dataset Information

Oral Tolerance Induction to Newly Introduced Allergen is Favored by a Transforming Growth Factor-?-Enriched Formula.

ABSTRACT: 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-? (TGF-?) plays a key role in immune tolerance, we tested whether an infant formula enriched with TGF-? would improve oral tolerance induction. A partially hydrolyzed whey protein-based formula was enriched with cow's-milk-derived TGF-? (TGF-?-enriched formula) by adding a specific whey protein isolate (WPI). The manufacturing process was optimized to achieve a concentration of TGF-? 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-?-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-?-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-?-enriched formula. In conclusion, oral supplementation with cow's-milk-derived TGF-? decreased allergic responses to newly introduced allergens and thus reduced the risk of developing food allergy.

SUBMITTER: Holvoet S

PROVIDER: S-EPMC6769637 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

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Oral Tolerance Induction to Newly Introduced Allergen is Favored by a Transforming Growth Factor-β-Enriched Formula.

Holvoet Sébastien S Perrot Marie M de Groot Nanda N Prioult Guénolée G Mikogami Takashi T Verhasselt Valérie V Nutten Sophie S

Nutrients 20190913 9

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 pro ...[more]

PMID: 31540231

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Project description:Multiple sclerosis (MS) is an autoimmune disease that attacks myelinated axons in the central nervous system. Induction of oral tolerance is a potent mechanism to prevent autoimmunity. The food yeast Candida utilis was used to test the therapeutic potential of oral tolerance induction in an animal model of human multiple sclerosis (MS). We constructed a C. utilis strain, which displays a fusion peptide composed of the encephalitogenic MOG35-55 peptide and the C. utilis Gas1 cell wall protein on its surface.By immunizing mice with MOG35-55 peptide experimental autoimmune encephalomyelitis (EAE) was induced in a mouse model. Feeding of mice with C. utilis that expresses MOG35-55 peptide on its surface was started seven days prior to immunization and was continued for ten days. Control animals were treated with wild-type fungus or left untreated. Untreated mice developed first clinical symptoms ten days post immunization (p. i.) with an ascending paralysis reaching maximal clinical disability at day 18 to 20 p. i.. Treatment with the wild-type strain demonstrated comparable clinical symptoms. In contrast, oral gavage of MOG35-55-presenting fungus ameliorated the development of EAE. In addition, incidence as well as maximal clinical disease severity were significantly reduced. Interestingly, reduction of disease severity also occurred in animals treated with heat-inactivated C. utilis cells indicating that tolerance induction was independent of fungal viability. Better disease outcome correlated with reduced demyelination and cellular inflammation in the spinal cord, lower T cell proliferation against rechallenge with MOG35-55 and more regulatory T cells in the lymph nodes. Our data demonstrate successful that using the food approved fungus C. utilis presenting the immunogenic MOG35-55 peptide on its surface induced an oral tolerance against this epitope in EAE. Further studies will reveal the nature and extent of an anti-inflammatory environment established by the treatment that prevents the development of an autoimmune disorder affecting the CNS.

Dataset Information

Oral Tolerance Induction to Newly Introduced Allergen is Favored by a Transforming Growth Factor-?-Enriched Formula.

Publications

Oral Tolerance Induction to Newly Introduced Allergen is Favored by a Transforming Growth Factor-β-Enriched Formula.

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