Intestinal Epithelium-Derived Galectin-9 Is Involved in the Immunomodulating Effects of Nondigestible Oligosaccharides

• Published in: Journal of innate immunity 2013-01, Vol.5 (6), p.625-638
• Main Authors: de Kivit, Sander, Kraneveld, Aletta D., Knippels, Leon M.J., van Kooyk, Yvette, Garssen, Johan, Willemsen, Linette E.M.
• Format: Article
• Language: English
• Subjects: Allergic diseases; Antigen-Presenting Cells - immunology; Antigen-Presenting Cells - metabolism; Bifidobacterium - genetics; Bifidobacterium - physiology; Bifidobacterium breve; Cell Line; Cells, Cultured; Coculture Techniques; DNA, Bacterial - immunology; DNA, Bacterial - pharmacology; Epithelial Cells - immunology; Epithelial Cells - metabolism; Flow Cytometry; Galectins - immunology; Galectins - metabolism; HT29 Cells; Humans; Immunomodulation - drug effects; Immunomodulation - immunology; Interferon-gamma - immunology; Interferon-gamma - metabolism; Interleukin-10 - immunology; Interleukin-10 - metabolism; Intestinal Mucosa - immunology; Intestinal Mucosa - metabolism; Leukocytes, Mononuclear - immunology; Leukocytes, Mononuclear - metabolism; Oligosaccharides - immunology; Oligosaccharides - pharmacology; Research Article; T-Lymphocytes, Regulatory - immunology; T-Lymphocytes, Regulatory - metabolism; Th1 Cells - immunology; Th1 Cells - metabolism; Toll-Like Receptor 9 - immunology; Toll-Like Receptor 9 - metabolism
• ISSN: 1662-811X; 1662-8128
• DOI: 10.1159/000350515

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 T h 1 and regulatory T-cell (T reg ) 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 T h 1 and T reg 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 T reg and T h 1 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 T h 1 and T reg polarization and may be a promising target to prevent or treat allergic disease.