TY - JOUR
T1 - 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
AU - Ayechu-Muruzabal, Veronica
AU - Overbeek, Saskia A.
AU - Kostadinova, Atanaska I.
AU - Stahl, Bernd
AU - Garssen, Johan
AU - Van’T Land, Belinda
AU - Willemsen, Linette E.M.
PY - 2020/5/1
Y1 - 2020/5/1
N2 - 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 20-fucosyllactose (20-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/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 20-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-β1 of CpG-exposed IEC. Only galectin-9 correlated with all modified immune parameters and TGF-β1 secretion. MoDCs exposed to 20-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 20-FL and GF could contribute to the mucosal immune development by supporting the e_ect of microbial CpG DNA associated with the modulation of epithelial galectin and TGF-β1 secretion.
AB - 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 20-fucosyllactose (20-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/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 20-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-β1 of CpG-exposed IEC. Only galectin-9 correlated with all modified immune parameters and TGF-β1 secretion. MoDCs exposed to 20-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 20-FL and GF could contribute to the mucosal immune development by supporting the e_ect of microbial CpG DNA associated with the modulation of epithelial galectin and TGF-β1 secretion.
KW - 1,2'-fucosyllactose 2
KW - Dendritic cells 6
KW - Galectins 4
KW - Intestinal epithelial cells 5
KW - Mucosal immunity
KW - Non-digestible oligosaccharides 3
UR - http://www.scopus.com/inward/record.url?scp=85085157292&partnerID=8YFLogxK
U2 - 10.3390/biom10050784
DO - 10.3390/biom10050784
M3 - Article
C2 - 32438601
AN - SCOPUS:85085157292
SN - 2218-273X
VL - 10
JO - Biomolecules
JF - Biomolecules
IS - 5
M1 - 784
ER -