Improved Efficacy of Oral Immunotherapy Using Non-Digestible Oligosaccharides in a Murine Cow's Milk Allergy Model: A Potential Role for Foxp3+ Regulatory T Cells.
Front Immunol
; 8: 1230, 2017.
Article
em En
| MEDLINE
| ID: mdl-29033945
ABSTRACT
BACKGROUND:
Oral immunotherapy (OIT) is a promising therapeutic approach to treat food allergic patients. However, there are some concerns regarding its safety and long-term efficacy. The use of non-digestible oligosaccharides might improve OIT efficacy since they are known to directly modulate intestinal epithelial and immune cells in addition to acting as prebiotics.AIM:
To investigate whether a diet supplemented with plant-derived fructo-oligosaccharides (FOS) supports the efficacy of OIT in a murine cow's milk allergy model and to elucidate the potential mechanisms involved.METHODS:
After oral sensitization to the cow's milk protein whey, female C3H/HeOuJ mice were fed either a control diet or a diet supplemented with FOS (1% w/w) and received OIT (10 mg whey) 5 days a week for 3 weeks by gavage. Intradermal (i.d.) and intragastric (i.g.) challenges were performed to measure acute allergic symptoms and mast cell degranulation. Blood and organs were collected to measure antibody levels and T cell and dendritic cell populations. Spleen-derived T cell fractions (whole spleen- and CD25-depleted) were transferred to naïve recipient mice to confirm the involvement of regulatory T cells (Tregs) in allergy protection induced by OIT + FOS.RESULTS:
OIT + FOS decreased acute allergic symptoms and mast cell degranulation upon challenge and prevented the challenge-induced increase in whey-specific IgE as observed in sensitized mice. Early induction of Tregs in the mesenteric lymph nodes (MLN) of OIT + FOS mice coincided with reduced T cell responsiveness in splenocyte cultures. CD25 depletion in OIT + FOS-derived splenocyte suspensions prior to transfer abolished protection against signs of anaphylaxis in recipients. OIT + FOS increased serum galectin-9 levels. No differences in short-chain fatty acid (SCFA) levels in the cecum were observed between the treatment groups. Concisely, FOS supplementation significantly improved OIT in the acute allergic skin response, %Foxp3+ Tregs and %LAP+ Th3 cells in MLN, and serum galectin-9 levels.CONCLUSION:
FOS supplementation improved the efficacy of OIT in cow's milk allergic mice. Increased levels of Tregs in the MLN and abolished protection against signs of anaphylaxis upon transfer of CD25-depleted cell fractions, suggest a role for Foxp3+ Tregs in the protective effect of OIT + FOS.
Texto completo:
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Coleções:
01-internacional
Base de dados:
MEDLINE
Idioma:
En
Revista:
Front Immunol
Ano de publicação:
2017
Tipo de documento:
Article
País de afiliação:
Holanda