4.7 Article

Protective Effects of ALDH1A Enzyme Inhibition on Helicobacter-Induced Colitis in Smad3-/- Mice are Associated with Altered α4ss7 Integrin Expression on Activated T Cells

期刊

NUTRIENTS
卷 12, 期 10, 页码 -

出版社

MDPI
DOI: 10.3390/nu12102927

关键词

retinoic acid; ALDH1A enzymes; immunity; inflammatory bowel disease; mouse model

资金

  1. National Institutes of Health [R56DK110239-01A1, K01OD021420]

向作者/读者索取更多资源

Many inflammatory bowel disease (IBD) patients require surgical intervention due to limited pharmacological treatment options. Antibodies targeting alpha 4ss7, a gut-homing integrin, are one of the most promising IBD treatments. As retinoic acid (RA) regulates expression of gut-homing proteins including alpha 4ss7 integrin, we tested if ALDH1A enzymes in the RA synthesis pathway could be targeted for IBD treatment using a potent inhibitor, WIN 18,446. Age- and sex-matched Smad3(-/-) mice were fed a diet with and without WIN 18,446 for 3 weeks before triggering inflammation with Helicobacter bilis infection. Colitis was evaluated by histopathology one week following the IBD trigger, and T cell subsets were evaluated before and after the IBD trigger. WIN 18,446 treatment significantly reduced IBD severity in Smad3(-/-) mice and reduced expression of alpha 4ss7 integrin on multiple activated CD4(+) T cell subsets. This change was associated with increased ratios of induced regulatory T cells to Th17 cells during the inflammatory response in the draining lymph nodes. These studies indicate that RA reduction via ALDH1A enzyme inhibition is a potential new target for IBD treatment. Further studies are needed to examine its effects on other types of immune cells, to evaluate the efficacy window for this target, and to determine its efficacy in other animal models of IBD.

作者

我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。

评论

主要评分

4.7
评分不足

次要评分

新颖性
-
重要性
-
科学严谨性
-
评价这篇论文

推荐

暂无数据
暂无数据