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Exposure of Intestinal Epithelial Cells to 2'-Fucosyllactose and CpG Enhances Galectin Release and Instructs Dendritic Cells to Drive Th1 and Regulatory-Type Immune Development.

ABSTRACT: Intestinal epithelial cells (IEC) release immunomodulatory galectins upon exposure to CpG DNA (mimicking bacterial triggers) and short-chain galacto- and long-chain fructo-oligosaccharides (GF). This study aims to investigate the immunomodulatory properties of 2'-fucosyllactose (2'-FL), a non-digestible oligosaccharide (NDO) abundantly present in human milk, using a co-culture model developed to study the crosstalk between IEC and innate and adaptive immune cells. IECs, co-cultured with ?CD3/CD28-activated peripheral blood mononuclear cells (PBMC), were apically exposed to NDOs and CpG, washed and co-cultured with immature monocyte-derived dendritic cells (moDC). Subsequently, moDC were co-cultured with naïve CD4+ T-cells. In the presence of CpG, both 2'-FL or GF-exposed IEC enhanced Th1-type IFN? and regulatory IL-10 secretion of PBMCs, compared to CpG alone, while Th2-type IL-13 was reduced. Both NDOs increased IEC-derived galectin-3, -4, -9 and TGF-?1 of CpG-exposed IEC. Only galectin-9 correlated with all modified immune parameters and TGF-?1 secretion. MoDCs exposed to 2'-FL and CpG-conditioned IEC instructed IFN? and IL-10 secretion by CD4+ T-cells, suggesting the development of a regulatory Th1 response. These results reveal that 2'-FL and GF could contribute to the mucosal immune development by supporting the effect of microbial CpG DNA associated with the modulation of epithelial galectin and TGF-?1 secretion.

SUBMITTER: Ayechu-Muruzabal V

PROVIDER: S-EPMC7278199 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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Exposure of Intestinal Epithelial Cells to 2'-Fucosyllactose and CpG Enhances Galectin Release and Instructs Dendritic Cells to Drive Th1 and Regulatory-Type Immune Development.

Ayechu-Muruzabal Veronica V Overbeek Saskia A SA Kostadinova Atanaska I AI Stahl Bernd B Garssen Johan J Van't Land Belinda B Willemsen Linette E M LEM

Biomolecules 20200519 5

Intestinal epithelial cells (IEC) release immunomodulatory galectins upon exposure to CpG DNA (mimicking bacterial triggers) and short-chain galacto- and long-chain fructo-oligosaccharides (GF). This study aims to investigate the immunomodulatory properties of 2'-fucosyllactose (2'-FL), a non-digestible oligosaccharide (NDO) abundantly present in human milk, using a co-culture model developed to study the crosstalk between IEC and innate and adaptive immune cells. IECs, co-cultured with αCD3/CD2 ...[more]

PMID: 32438601

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Project description:BackgroundShort-chain galacto- and long-chain fructo-oligosaccharides (scGOS/lcFOS) and CpG-ODN affect intestinal epithelial cells (IEC). Epithelial IL1α may contribute to allergic sensitization via autocrine mediator release affecting dendritic cells (DC). We studied whether IL1α contributes to Th2-associated mediator release by activated IEC and IEC/DC cocultures and possible modulation by scGOS/lcFOS±CpG-ODN.MethodsSolid phase or transwell cultured IEC were preincubated with IL1α and/or IFNγ/TNFα 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.ResultsIL1α tended to enhance IL25 and enhanced IL33 and CCL20 release by IEC, while IL1α or TNFα or IFNγ enhanced CCL22. These were all further increased upon combined exposure of IFNγ/TNFα±IL1α 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 IL1α or IFNγ/TNFα, respectively, and a synergistic increase was observed upon combined exposure of IFNγ/TNFα and IL1α. Furthermore, IFNγ was found to enhance galectin-9 secretion, which was more pronounced in IFNγ/TNFα±IL1α-exposed IEC and coincided with TGFβ increase. Epithelial CpG-ODN exposure further increased CCL20, while reducing CCL22 release by IFNγ/TNFα/IL1α-activated IEC; however, scGOS/lcFOS suppressed both. Combined scGOS/lcFOS and CpG-ODN reduced CCL22, while CCL20 and regulatory galectin-9 and TGFβ remained high in the supernatant of IFNγ/TNFα/IL1α-activated IEC and the following IEC/DC coculture. ccDC of scGOS/lcFOS- and CpG-ODN-exposed IFNγ/TNFα/IL1α-activated IEC increased IFNγ, IL10, TGFβ, and galectin-9 secretion in the MLR compared to ccDC exposed to control-activated IEC.ConclusionIL1α enhanced CCL20 and Th2-associated CCL22 release by IFNγ/TNFα-activated IEC. Combined scGOS/lcFOS and CpG-ODN exposure suppressed CCL22, while maintaining high CCL20, TGFβ, and galectin-9 concentrations. In addition, ccDC derived from this IEC/DC coculture enhanced Th1 and regulatory mediator secretion mimicking known in vivo effects.

Dataset Information

Exposure of Intestinal Epithelial Cells to 2'-Fucosyllactose and CpG Enhances Galectin Release and Instructs Dendritic Cells to Drive Th1 and Regulatory-Type Immune Development.

Publications

Exposure of Intestinal Epithelial Cells to 2'-Fucosyllactose and CpG Enhances Galectin Release and Instructs Dendritic Cells to Drive Th1 and Regulatory-Type Immune Development.

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