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Original Article
- Inflammatory bowel diseases
- A glycolipid adjuvant, 7DW8-5, provides a protective effect against colonic inflammation in mice by the recruitment of CD1d-restricted natural killer T cells
- Chansu Lee, Sung Noh Hong, Young-Ho Kim
- Intest Res 2020;18(4):402-411. Published online April 8, 2020
- DOI: https://doi.org/10.5217/ir.2019.00132
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Abstract
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Supplementary Material
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ePub - Background/Aims
The modulation of CD1d-restricted natural killer T (NKT) cells by glycolipids has been considered as a potential therapy against immunologic diseases, including inflammatory bowel disease. A recently identified a glycolipid analog, 7DW8-5, which is derived from α-galactosylceramide (α-GalCer), is as much as 100-fold more active at stimulating both human and mice NKT cells when compared to α-GalCer. We explored the effects of 7DW8-5 in mouse models of acute and chronic colitis.
Methods
We investigated the effects of 7DW8-5 on intestinal inflammation by assessing the effects of 7dW8-5 on a murine dextran sulfate sodium (DSS)-induced acute colitis model and a chronic colitis-associated tumor model.
Results
The acute DSS-induced colitis model showed a dose-dependent response to 7DW8-5, as mice administered 7DW8-5 showed a significant improvement in DSS-induced colitis based on their disease activity index, histologic analysis, and serum C-reactive protein levels, when compared to mice administered vehicle alone. However, DSS-induced colitis in CD1d-KO mice showed no response to 7DW8-5. A fluorescence-activating cell sorting analysis revealed an increase in NKT cells in colonic tissues of 7DW8-5-treated mice. RNA-seq and real-time quantitative polymerase chain reaction showed a significant increase in the expression of interleukin (IL)-4, IL-13, and interferon-gamma in 7DW8-5-treated mice. In addition, 7DW8-5 treatment reduced colitis-associated tumor development in an azoxymethane/DSS mouse model.
Conclusions
7DW8-5 activates NKT cells through CD1d and provides a protective effect against intestinal inflammation in mice. Therefore, 7DW8-5 may be a promising therapeutic agent for treatment of inflammatory bowel disease. -
Citations
Citations to this article as recorded by
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Journal of Agricultural and Food Chemistry.2022; 70(30): 9463. CrossRef - Sex-Specific Differences in Cytokine Induction by the Glycolipid Adjuvant 7DW8-5 in Mice
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