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
BackgroundOral 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 intest...
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Frontiers Media S.A.
2017-09-01
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Online Access: | http://journal.frontiersin.org/article/10.3389/fimmu.2017.01230/full |
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Article |
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DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Marlotte M. Vonk Marlotte M. Vonk Mara A. P. Diks Laura Wagenaar Joost J. Smit Raymond H. H. Pieters Johan Garssen Johan Garssen Betty C. A. M. van Esch Betty C. A. M. van Esch Léon M. J. Knippels Léon M. J. Knippels |
spellingShingle |
Marlotte M. Vonk Marlotte M. Vonk Mara A. P. Diks Laura Wagenaar Joost J. Smit Raymond H. H. Pieters Johan Garssen Johan Garssen Betty C. A. M. van Esch Betty C. A. M. van Esch Léon M. J. Knippels Léon M. J. Knippels 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 Frontiers in Immunology cow’s milk allergy oral immunotherapy desensitization non-digestible oligosaccharides regulatory T cell butyric acid |
author_facet |
Marlotte M. Vonk Marlotte M. Vonk Mara A. P. Diks Laura Wagenaar Joost J. Smit Raymond H. H. Pieters Johan Garssen Johan Garssen Betty C. A. M. van Esch Betty C. A. M. van Esch Léon M. J. Knippels Léon M. J. Knippels |
author_sort |
Marlotte M. Vonk |
title |
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 |
title_short |
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 |
title_full |
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 |
title_fullStr |
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 |
title_full_unstemmed |
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 |
title_sort |
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 |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Immunology |
issn |
1664-3224 |
publishDate |
2017-09-01 |
description |
BackgroundOral 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.AimTo 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.MethodsAfter 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.ResultsOIT + 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.ConclusionFOS 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. |
topic |
cow’s milk allergy oral immunotherapy desensitization non-digestible oligosaccharides regulatory T cell butyric acid |
url |
http://journal.frontiersin.org/article/10.3389/fimmu.2017.01230/full |
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doaj-360d5db9e12e4970b763faf56bba18802020-11-25T00:50:05ZengFrontiers Media S.A.Frontiers in Immunology1664-32242017-09-01810.3389/fimmu.2017.01230298174Improved Efficacy of Oral Immunotherapy Using Non-Digestible Oligosaccharides in a Murine Cow’s Milk Allergy Model: A Potential Role for Foxp3+ Regulatory T CellsMarlotte M. Vonk0Marlotte M. Vonk1Mara A. P. Diks2Laura Wagenaar3Joost J. Smit4Raymond H. H. Pieters5Johan Garssen6Johan Garssen7Betty C. A. M. van Esch8Betty C. A. M. van Esch9Léon M. J. Knippels10Léon M. J. Knippels11Faculty of Science, Department of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, NetherlandsImmunology Platform, Nutricia Research, Utrecht, NetherlandsFaculty of Science, Department of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, NetherlandsFaculty of Veterinary Medicine, Department of Immunotoxicology, Institute for Risk Assessment Sciences, Utrecht University, Utrecht, NetherlandsFaculty of Veterinary Medicine, Department of Immunotoxicology, Institute for Risk Assessment Sciences, Utrecht University, Utrecht, NetherlandsFaculty of Veterinary Medicine, Department of Immunotoxicology, Institute for Risk Assessment Sciences, Utrecht University, Utrecht, NetherlandsFaculty of Science, Department of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, NetherlandsImmunology Platform, Nutricia Research, Utrecht, NetherlandsFaculty of Science, Department of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, NetherlandsImmunology Platform, Nutricia Research, Utrecht, NetherlandsFaculty of Science, Department of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, NetherlandsImmunology Platform, Nutricia Research, Utrecht, NetherlandsBackgroundOral 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.AimTo 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.MethodsAfter 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.ResultsOIT + 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.ConclusionFOS 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.http://journal.frontiersin.org/article/10.3389/fimmu.2017.01230/fullcow’s milk allergyoral immunotherapydesensitizationnon-digestible oligosaccharidesregulatory T cellbutyric acid |