A glycolipid adjuvant, 7DW8-5, provides a protective effect against colonic inflammation in mice by the recruitment of CD1d-restricted natural killer T cellsopen access
- Authors
- Lee, Chansu; Hong, Sung Noh; Kim, Young-Ho
- Issue Date
- Oct-2020
- Publisher
- KOREAN ASSOC STUDY INTESTINAL DISEASES
- Keywords
- 7DW8-5; Alpha-galactosylceramide; Natural killer T-cells; Dextran sulfate sodium; Inflammatory bowel disease
- Citation
- INTESTINAL RESEARCH, v.18, no.4, pp 402 - +
- Indexed
- SCOPUS
ESCI
KCI
- Journal Title
- INTESTINAL RESEARCH
- Volume
- 18
- Number
- 4
- Start Page
- 402
- End Page
- +
- URI
- https://scholarworks.bwise.kr/skku/handle/2021.sw.skku/98429
- DOI
- 10.5217/ir.2019.00132
- ISSN
- 1598-9100
2288-1956
- Abstract
- 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 alpha-galactosylceramide (alpha-GalCer), is as much as 100-fold more active at stimulating both human and mice NKT cells when compared to alpha-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.
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Collections - Medicine > Department of Medicine > 1. Journal Articles
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