Apical TLR ligation of intestinal epithelial cells drives a Th1-polarized regulatory or inflammatory type effector response in vitro

Kivit, Sander de; Hoffen, Els van; Korthagen, N.M.; Garssen, Johan; Willemsen, Linette E. M.

doi:10.1016/j.imbio.2010.08.005

Cited by 51 publications

(63 citation statements)

References 38 publications

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“…Studies using a similar coculture model as was used in our study demonstrated that apical stimulation of TLR9 and TLR4 on human epithelial cell lines enhanced the secretion of IL-12 in underlying peripheral blood mononuclear cells (PBMCs) via an epithelial cell-mediated mechanism (3,24). In these studies, TLR4 ligation of epithelial cells drove an inflamma- tory response, while apical stimulation of TLR9 drove a regulatory Th1 effector immune response (3).…”

Section: Discussionmentioning

confidence: 67%

Intestinal Epithelial Cells Modulate Antigen-Presenting Cell Responses to Bacterial DNA

et al. 2012

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Section: Discussionmentioning

confidence: 67%

Intestinal Epithelial Cells Modulate Antigen-Presenting Cell Responses to Bacterial DNA

et al. 2012

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“…We hypothesized that DNA of B. breve M-16V may activate TLR9 on IEC as apical TLR9 ligation of IEC can induce a regulatory-type T h 1 response [11]. IEC apically exposed to purified DNA from B. breve M-16V or a synthetic TLR9 ligand enhanced IFN-γ secretion by activated PBMC, which was potentiated by scGOS/lcFOS (fig.…”

Section: Resultsmentioning

confidence: 99%

“…Culture of human IEC lines (HT-29 and T84 cells), isolation of human PBMC and transwell cocultures were performed as previously described [11]. In short, HT-29 or T84 cells were grown till confluence on transwell insert filters (Corning, N.Y., USA).…”

Section: Methodsmentioning

confidence: 99%

“…Epithelial TLR9 ligation by unmethylated bacterial CpG DNA was found to induce tolerance to subsequent TLR stimuli, illustrating its involvement in the maintenance of intestinal homeostasis [10]. In vitro, IEC modulate effector immune responses in a polarized fashion as apical, but not basolateral TLR9 ligand exposure enhances IFN-γ and IL-10 secretion, while suppressing IL-13 production by peripheral blood mononuclear cells (PBMC) [11]. In a murine model of peanut allergy, oral administration of TLR9 agonists prevented allergy, linking TLR9 activation to a reduction in allergic diseases [12].…”

Section: Introductionmentioning

confidence: 99%

“…We have previously shown that dietary intervention using scGOS/lcFOS in combination with B. breve M-16V enhances serum galectin-9 levels. To this end, we studied the effects of IEC exposure to scGOS/lcFOS and TLR9 ligand on human PBMC in an in vitro coculture system [11]. We demonstrate that galectin-9 is expressed and secreted by IEC upon apical exposure to TLR9 ligand and scGOS/lcFOS, which drives a T h 1/T reg response.…”

Section: Introductionmentioning

confidence: 99%

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

Kivit¹,

Kraneveld²,

Knippels³

et al. 2013

J Innate Immun

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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_h1 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_h1 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_h1 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_h1 and T_reg polarization and may be a promising target to prevent or treat allergic disease.

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Nondigestible oligosaccharides exert nonprebiotic effects on intestinal epithelial cells enhancing the immune response via activation of TLR4‐NFκB

Ortega‐González

Ocón

Romero‐Calvo

et al. 2013

Molecular Nutrition Food Res

103

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show abstract

Apical TLR ligation of intestinal epithelial cells drives a Th1-polarized regulatory or inflammatory type effector response in vitro

Cited by 51 publications

References 38 publications

Intestinal Epithelial Cells Modulate Antigen-Presenting Cell Responses to Bacterial DNA

Intestinal Epithelial Cells Modulate Antigen-Presenting Cell Responses to Bacterial DNA

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

Nondigestible oligosaccharides exert nonprebiotic effects on intestinal epithelial cells enhancing the immune response via activation of TLR4‐NFκB

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