RELMβ设定了微生物组依赖的口服耐受性的值
Emmanuel Stephen-Victor1,2, Gavin A Kuziel2,3,4,5, Monica Martinez-Blanco1,2
1Division of Immunology, Boston Children's Hospital, Boston, MA, USA.
Nature
|January 22, 2025
概括
通过改变肠道微生物组,阻抗类分子β (RELMβ) 破坏了口服耐受性. 阻断RELMβ恢复了耐受性,为预防食物过敏提供了潜在的策略.
科学领域:
- 免疫学
- 微生物组研究
- 胃肠病学
背景情况:
- 食物过敏 (FA) 涉及有害的2型免疫反应,但耐受性机制尚不清楚.
- 对饮食抗原的口服耐受性对于预防FA和过敏反应至关重要.
- 玻璃杯细胞衍生的抗体样分子β (RELMβ) 参与免疫调节.
研究的目的:
- 研究RELMβ在调节口服抗原中的作用.
- 阐明RELMβ影响食物耐受性和FA发展的机制.
- 确定FA预防和治疗的潜在治疗点.
主要方法:
- 使用FA和基因删除研究的小鼠模型 (RELMβ淘汰).
- 在FA患者和小鼠模型中分析了血清RELMβ水平.
- 研究RELMβ对肠道微生物组合和功能的影响 (内代谢).
- 评估了醇衍生物和RORγt+调节性T细胞在耐受性方面的作用.
- 评估了RELMβ对抗的治疗潜力.
主要成果:
- 在FA患者和小鼠模型中,RELMβ升高.
- 从FA,IgE生产和过敏反应中保护RELMβ删除的小鼠.
- RELMβ通过消耗产生印醇的乳杆菌和Alistipes来破坏口服耐受性.
- 印醇衍生物通过基碳水化合物受体激活促进FA保护的RORγt+ Treg细胞.
- 在断奶期间的RELMβ对抗在敏感小鼠中恢复了耐受性和预防了FA.
结论:
- RELMβ是口服耐受性的关键调节剂,介导肠道免疫上皮电路.
- 通过微生物组编辑来影响RELMβ的功能,影响适应性免疫的先天控制.
- 针对RELMβ - 微生物组 - 印度尔 - 特雷格轴提供了FA预防和治疗的新策略.
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