Dataset Information

Combined Exposure of Activated Intestinal Epithelial Cells to Nondigestible Oligosaccharides and CpG-ODN Suppresses Th2-Associated CCL22 Release While Enhancing Galectin-9, TGF?, and Th1 Polarization.

ABSTRACT:

Background

Short-chain galacto- and long-chain fructo-oligosaccharides (scGOS/lcFOS) and CpG-ODN affect intestinal epithelial cells (IEC). Epithelial IL1? may contribute to allergic sensitization via autocrine mediator release affecting dendritic cells (DC). We studied whether IL1? contributes to Th2-associated mediator release by activated IEC and IEC/DC cocultures and possible modulation by scGOS/lcFOS±CpG-ODN.

Methods

Solid phase or transwell cultured IEC were preincubated with IL1? and/or IFN?/TNF? for 6?h. The transwell IEC were also apically exposed to scGOS/lcFOS±CpG-ODN for 6?h, washed, and re-exposed, while cocultured with immature moDC (ccDC) for 48?h. These ccDC were subsequently added to allogeneic naïve T cells (MLR). IEC- and/or DC-derived mediators and T cell cytokines were measured.

Results

IL1? tended to enhance IL25 and enhanced IL33 and CCL20 release by IEC, while IL1? or TNF? or IFN? enhanced CCL22. These were all further increased upon combined exposure of IFN?/TNF?±IL1? coinciding with increased IL33 secretion in the solid phase culture. In the transwell, IL25 and IL33 remained under detection, while CCL20 and CCL22 were induced by IL1? or IFN?/TNF?, respectively, and a synergistic increase was observed upon combined exposure of IFN?/TNF? and IL1?. Furthermore, IFN? was found to enhance galectin-9 secretion, which was more pronounced in IFN?/TNF?±IL1?-exposed IEC and coincided with TGF? increase. Epithelial CpG-ODN exposure further increased CCL20, while reducing CCL22 release by IFN?/TNF?/IL1?-activated IEC; however, scGOS/lcFOS suppressed both. Combined scGOS/lcFOS and CpG-ODN reduced CCL22, while CCL20 and regulatory galectin-9 and TGF? remained high in the supernatant of IFN?/TNF?/IL1?-activated IEC and the following IEC/DC coculture. ccDC of scGOS/lcFOS- and CpG-ODN-exposed IFN?/TNF?/IL1?-activated IEC increased IFN?, IL10, TGF?, and galectin-9 secretion in the MLR compared to ccDC exposed to control-activated IEC.

Conclusion

IL1? enhanced CCL20 and Th2-associated CCL22 release by IFN?/TNF?-activated IEC. Combined scGOS/lcFOS and CpG-ODN exposure suppressed CCL22, while maintaining high CCL20, TGF?, and galectin-9 concentrations. In addition, ccDC derived from this IEC/DC coculture enhanced Th1 and regulatory mediator secretion mimicking known in vivo effects.

SUBMITTER: Overbeek SA

PROVIDER: S-EPMC6683774 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Combined Exposure of Activated Intestinal Epithelial Cells to Nondigestible Oligosaccharides and CpG-ODN Suppresses Th2-Associated CCL22 Release While Enhancing Galectin-9, TGF<i>β</i>, and Th1 Polarization.

Overbeek Saskia A SA Kostadinova Atanaska I AI Boks Martine A MA Hayen Simone M SM de Jager Wilco W Van't Land Belinda B Knippels Leon M LM Garssen Johan J Willemsen Linette E M LEM

Mediators of inflammation 20190725

<h4>Background</h4>Short-chain galacto- and long-chain fructo-oligosaccharides (scGOS/lcFOS) and CpG-ODN affect intestinal epithelial cells (IEC). Epithelial IL1<i>α</i> may contribute to allergic sensitization via autocrine mediator release affecting dendritic cells (DC). We studied whether IL1<i>α</i> contributes to Th2-associated mediator release by activated IEC and IEC/DC cocultures and possible modulation by scGOS/lcFOS±CpG-ODN.<h4>Methods</h4>Solid phase or transwell cultured IEC were pre ...[more]

PMID: 31427886

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