Intestinal epithelium-derived galectin-9 is involved in the immunomodulating effects of nondigestible oligosaccharides

Sander De Kivit, Aletta D. Kraneveld, Leon M.J. Knippels, Yvette Van Kooyk, Johan Garssen, Linette E.M. Willemsen

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Dietary intervention using nondigestible oligosaccharides, short-chain galacto-oligosaccharides (scGOS)/long-chain fructo-oligosaccharides (lcFOS), in combination with Bifido-bacterium breve M-16V prevents allergic disease involving galectin-9. In addition, apical TLR9 signaling contributes to intestinal homeostasis. We studied the contribution of galectin-9 secreted by intestinal epithelial cells (IEC; HT-29 and T84) in Th1 and regulatory T-cell (Treg) polarization in vitro. IEC were grown in transwell filters, cocultured with CD3/CD28-activated human peripheral blood mononuclear cells (PBMC) and apically exposed to genomic DNA derived from B. breve M-16V or synthetic TLR9 ligand in the absence or presence of scGOS/lcFOS. Cytokine production and T-cell phenotype were determined and galectin expression by IEC was assessed. Galectin-9 was neutralized using lactose or a TIM-3-Fc fusion protein. IEC exposed to DNA from B. breve M-16V or TLR9 ligand in the presence of scGOS/lcFOS enhanced IFN-γ secretion by PBMC and increased the percentage of Th1 and Tregcells. Expression and secretion of galectin-9 by IEC was increased and neutralization of galectin-9 prevented the induction of IFN-γ secretion and also suppressed the production of IL-10 by PBMC. Furthermore, we show that galectin-9 induces Tregand Th1 polarization through interaction with antigen-presenting cells. Our findings show that galectin-9 secreted by IEC apically exposed to TLR9 ligand in the presence of scGOS/lcFOS is involved in Th1 and Tregpolarization and may be a promising target to prevent or treat allergic disease. Copyright © 2013 S. Karger AG, Basel.
Original languageEnglish
Pages (from-to)625-638
Number of pages14
JournalJournal of Innate Immunity
Volume5
Issue number6
DOIs
Publication statusPublished - 1 Nov 2013

Keywords

  • Galectin-9
  • Intestinal epithelial cells
  • Nondigestible oligosaccharides
  • Regulatory T cells
  • Th1 cells
  • TLR9
  • CD28 antigen
  • CD3 antigen
  • CD4 antigen
  • CD45RA antigen
  • ecalectin
  • fructose oligosaccharide
  • galactose oligosaccharide
  • galectin 4
  • gamma interferon
  • genomic DNA
  • hybrid protein
  • interleukin 10
  • interleukin 12
  • interleukin 13
  • interleukin 17
  • interleukin 6
  • lactose
  • long chain fatty acid
  • oligosaccharide
  • short chain fatty acid
  • toll like receptor 9
  • tumor necrosis factor alpha
  • antigen presenting cell
  • article
  • Bifidobacterium breve
  • CD4+ T lymphocyte
  • cell differentiation
  • coculture
  • cytokine production
  • cytokine release
  • dendritic cell
  • gene expression
  • human
  • human cell
  • immunomodulation
  • intestine epithelium cell
  • mixed lymphocyte culture
  • monocyte
  • nonhuman
  • peripheral blood mononuclear cell
  • phenotype
  • polarization
  • priority journal
  • regulatory T lymphocyte
  • signal transduction
  • Th1 cell
  • Th2 cell

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