Tan Jian, McKenzie Craig, Vuillermin Peter J, Goverse Gera, Vinuesa Carola G, Mebius Reina E, Macia Laurence, Mackay Charles R
Infection and Immunity Program, Monash Biomedicine Discovery Institute and Department of Biochemistry and Molecular Biology, Monash University, Clayton, VIC 3800, Australia.
School of Medicine, Deakin University, Waurn Ponds, VIC 3216, Australia.
Cell Rep. 2016 Jun 21;15(12):2809-24. doi: 10.1016/j.celrep.2016.05.047.
The incidence of food allergies in western countries has increased dramatically in recent decades. Tolerance to food antigens relies on mucosal CD103(+) dendritic cells (DCs), which promote differentiation of regulatory T (Treg) cells. We show that high-fiber feeding in mice improved oral tolerance and protected from food allergy. High-fiber feeding reshaped gut microbial ecology and increased the release of short-chain fatty acids (SCFAs), particularly acetate and butyrate. High-fiber feeding enhanced oral tolerance and protected against food allergy by enhancing retinal dehydrogenase activity in CD103(+) DC. This protection depended on vitamin A in the diet. This feeding regimen also boosted IgA production and enhanced T follicular helper and mucosal germinal center responses. Mice lacking GPR43 or GPR109A, receptors for SCFAs, showed exacerbated food allergy and fewer CD103(+) DCs. Dietary elements, including fiber and vitamin A, therefore regulate numerous protective pathways in the gastrointestinal tract, necessary for immune non-responsiveness to food antigens.
近几十年来，西方国家食物过敏的发生率急剧上升。对食物抗原的耐受性依赖于黏膜CD103(+)树突状细胞（DCs），其可促进调节性T（Treg）细胞的分化。我们发现，给小鼠喂食高纤维食物可改善口服耐受性并预防食物过敏。高纤维饮食重塑了肠道微生物生态，并增加了短链脂肪酸（SCFAs）的释放，尤其是乙酸盐和丁酸盐。高纤维饮食通过增强CD103(+) DC中的视黄醛脱氢酶活性来增强口服耐受性并预防食物过敏。这种保护作用依赖于饮食中的维生素A。这种喂养方案还可促进IgA的产生，并增强T滤泡辅助细胞和黏膜生发中心反应。缺乏SCFAs受体GPR43或GPR109A的小鼠表现出更严重的食物过敏，且CD103(+) DC数量减少。因此，包括纤维和维生素A在内的饮食成分可调节胃肠道中的多种保护途径，这些途径对于对食物抗原的免疫无反应性是必需的。
