scholarly journals 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

Biomolecules ◽  
2020 ◽  
Vol 10 (5) ◽  
pp. 784 ◽  
Author(s):  
Veronica Ayechu-Muruzabal ◽  
Saskia A. Overbeek ◽  
Atanaska I. Kostadinova ◽  
Bernd Stahl ◽  
Johan Garssen ◽  
...  

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/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 IFNγ 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 2′-FL and CpG-conditioned IEC instructed IFNγ 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-β1 secretion.

iScience ◽  
2021 ◽  
pp. 103225
Author(s):  
Tomas Raul Wiche Salinas ◽  
Annie Gosselin ◽  
Laurence Raymond Marchand ◽  
Etiene Moreira Gabriel ◽  
Olivier Tastet ◽  
...  

2019 ◽  
Vol 5 ◽  
pp. 20-21
Author(s):  
T. Wiche Salinas ◽  
A. Gosselin ◽  
B. Mariana ◽  
H. Touil ◽  
Y. Zhang ◽  
...  

2017 ◽  
Vol 9 (6) ◽  
pp. 609-620 ◽  
Author(s):  
Sander de Kivit ◽  
Atanaska I. Kostadinova ◽  
JoAnn Kerperien ◽  
Veronica Ayechu Muruzabal ◽  
Mary E. Morgan ◽  
...  

Intestinal epithelial cells (IEC) drive regulatory T cell (Treg) responses by promoting the differentiation of aldehyde dehydrogenase (ALDH)-expressing CD103+ dendritic cells (DC). Apical stimulation of TLR9 by CpG DNA on IEC supports galectin-9 expression by IEC, which is promoted by short-chain galacto-oligosaccharides and long-chain fructo-oligosaccharides (GF). While galectin-9 can induce the maturation of monocyte-derived DC (moDC), the contribution of galectin-9 on the induction of ALDH activity in DC is not known. To this end, DC were stimulated with galectin-9, and ALDH activity and the expression of CD103 were assessed. ALDH activity was increased by moDC exposed to galectin-9, while the expression of CD103 remained unaltered. Galectin-9 secreted by IEC apically exposed to CpG DNA and GF enhanced ALDH activity, but not CD103 expression by moDC, which was abrogated upon galectin-9 neutralization. Similar observations were found in murine GM-CSF-cultured bone marrow-derived DC (BMDC). Using Flt3L-cultured BMDC and ex vivo murine splenic DC, it was observed that galectin-9 only enhanced ALDH activity in the presence of GM-CSF in CD103- cells. The induction of ALDH activity in BMDC was dependent on p38 and PI3K signaling. These data indicate a novel role for galectin-9 in modulating innate immunity by inducing ALDH activity in DC.


2014 ◽  
Vol 8 (1) ◽  
pp. 38-48 ◽  
Author(s):  
V Cerovic ◽  
S A Houston ◽  
J Westlund ◽  
L Utriainen ◽  
E S Davison ◽  
...  

2012 ◽  
Vol 93 (6) ◽  
pp. 580-588 ◽  
Author(s):  
Hua Yang ◽  
Elaine Y. Cheng ◽  
Vijay K. Sharma ◽  
Mila Lagman ◽  
Christina Chang ◽  
...  

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