title: Intestinal epithelium-derived galectin-9 is involved in the immunomodulating effects of nondigestible oligosaccharides.
abstract: Dietary intervention using nondigestible oligosaccharides, short-chain galacto-oligosaccharides (scGOS)/long-chain fructo-oligosaccharides (lcFOS), in combination with Bifidobacterium 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 Treg cells. 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 Treg and 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 Treg polarization and may be a promising target to prevent or treat allergic disease.
authors.affiliation: Division of Pharmacology, Utrecht Institute of Pharmaceutical Sciences, Faculty of Science, Utrecht University, Utrecht, The Netherlands.
authors.forename: Sander
authors.initials: S
authors.lastname: de Kivit
authors.forename: Aletta D
authors.initials: AD
authors.lastname: Kraneveld
authors.forename: Leon M J
authors.initials: LM
authors.lastname: Knippels
authors.forename: Yvette
authors.initials: Y
authors.lastname: van Kooyk
authors.forename: Johan
authors.initials: J
authors.lastname: Garssen
authors.forename: Linette E M
authors.initials: LE
authors.lastname: Willemsen
mesh_terms: D000938:Antigen-Presenting Cells / Q000276:immunology / Q000378:metabolism; D001644:Bifidobacterium / Q000235:genetics / Q000502:physiology; D002460:Cell Line; D002478:Cells, Cultured; D018920:Coculture Techniques; D004269:DNA, Bacterial / Q000276:immunology / Q000494:pharmacology; D004847:Epithelial Cells / Q000276:immunology* / Q000378:metabolism; D005434:Flow Cytometry; D037161:Galectins / Q000276:immunology* / Q000378:metabolism; D019073:HT29 Cells; D006801:Humans; D056747:Immunomodulation / Q000187:drug effects / Q000276:immunology*; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D016753:Interleukin-10 / Q000276:immunology / Q000378:metabolism; D007413:Intestinal Mucosa / Q000276:immunology* / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism; D009844:Oligosaccharides / Q000276:immunology* / Q000494:pharmacology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism; D051217:Toll-Like Receptor 9 / Q000276:immunology / Q000378:metabolism
chemical_list: D004269:DNA, Bacterial; D037161:Galectins; C105032:LGALS9 protein, human; D009844:Oligosaccharides; D051217:Toll-Like Receptor 9; D016753:Interleukin-10; D007371:Interferon-gamma