Dietary intervention with specific nondigestible oligosaccharides and Bifidobacterium breve M-16V support the development of tolerogenic DC

S. De Kivit, J. Kerperien, M.E. Morgan, A.I. Kostadinova, K. Bouwknegt, G.A. Hofman, B.C.A.M. Van Esch, L.M.J. Knippels, A.D. Kraneveld, L.E.M. Willemsen, J. Garssen

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Background: Dietary intervention using a combination of a specific non-digestible oligosaccharide mixture - containing shortchain galacto- and long-chain fructo-oligosaccharides (GF) in a 9:1 ratio - and Bifidobacterium breve M-16V (Bb; GF/Bb) is known to prevent the development of food allergic symptoms. We have indicated a potential protective role for intestinal epithelium- derived galectin-9 in suppressing mast cell degranulation in the gut mucosa. However, it is not known whether GF/Bb can modulate DC and T cell responses in the intestine. Method: Using an ovalbumin (OVA)- induced murine model for food allergy, we evaluated whether dietary intervention with GF/Bb during allergic sensitisation results in changes in DC and T cell subsets in the gut-associated lymphoid tissue. Supporting in vitro experiments were performed to evaluate the involvement of galectin-9 in DC conditioning and T cell polarisation. Results: Upon OVA challenge, an increase in CD11c+MHC-IImid cells was observed in the small intestinal lamina propria (SILP). In allergic mice, CD11c+MHC-IImid cells expressed lower levels of CD103, which was partially restored when mice were fed GF/Bb. Furthermore, CD11c+ cells in the SI-LP of allergic mice produce more IL-4, which was paralleled with an increase in CD69+GATA-3+ activated Th2 cells and reduced Foxp3+ Treg cells in the SI-LP. Dietary intervention with GF/Bb suppressed IL-4 production by SILP CD11c+ cells and restored the frequency of Th2 and Treg cells to the level of sham sensitised mice. Furthermore, OVA re-stimulation of splenocytes from allergic mice showed increased production of IL-4, IL-5 and IL-13. The presence of recombinant galectin-9 during OVA restimulation partially reduced the secretion of IL-4 and IL-5, but not IFN-c. Supporting in vitro experiments show that galectin- 9 secreted by IEC induces RALDH activity in human monocyte-derived DC. Furthermore, monocyte-derived DC conditioned with galectin-9 had increased capacity to induce functional Foxp3+ Treg cells. Conclusion: Dietary intervention using GF/Bb supports the generation of tolerogenic DC, resulting in reduced Th2-associated cytokine production and enhanced Treg polarisation. Galectin-9 secreted by IEC may be involved in conditioning DC to induce Treg cell differentiation.
Original languageEnglish
Pages (from-to)94
Number of pages1
JournalAllergy
Volume68
DOIs
Publication statusPublished - 1 Sept 2013

Keywords

  • oligosaccharide
  • ecalectin
  • interleukin 4
  • interleukin 5
  • ovalbumin
  • fructose oligosaccharide
  • transcription factor GATA 3
  • allergy
  • asthma
  • clinical immunology
  • Bifidobacterium breve
  • regulatory T lymphocyte
  • mouse
  • human
  • intestine
  • conditioning
  • monocyte
  • T lymphocyte
  • in vitro study
  • T lymphocyte subpopulation
  • Th2 cell
  • mucosa
  • food allergy
  • mast cell degranulation
  • intestine epithelium
  • murine model
  • food
  • intestine lymphatic tissue
  • cell differentiation
  • lamina propria
  • cytokine production
  • secretion (process)
  • stimulation

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