天生的淋巴细胞通过互白素-2 支持肠道中的调节性T细胞
Lei Zhou1,2,3, Coco Chu1,2,3, Fei Teng1,2,3
1Division of Gastroenterology, Joan and Sanford I. Weill Department of Medicine, Weill Cornell Medicine, Cornell University, New York, NY, USA.
Nature
|April 5, 2019
概括
互白素-2 (IL-2) 对肠道免疫非常重要. 第三组先天性淋巴细胞 (ILC3) 产生IL-2,它维持调节性T细胞 (Treg) 并防止炎症,这是克罗恩病中受损的途径.
科学领域:
- 免疫学
- 胃肠病学
- 微生物组研究
背景情况:
- 通过支持调节性T (Treg) 细胞,interleukin-2 (IL-2) 对于预防胃肠炎症至关重要.
- 低剂量IL-2治疗是炎症性肠病的潜在治疗方法.
- 在肠道中IL-2的细胞和分子来源尚不清楚.
研究的目的:
- 阐明小肠IL-2产生的细胞来源和调节途径.
- 研究IL-2在维持肠道免疫平衡和Treg细胞功能的作用.
- 探索这种途径在人类炎症性肠病中的相关性.
主要方法:
- 使用特定基因删除的小鼠模型来追踪IL-2的产生.
- 使用无偏见的分析来识别小肠中的IL-2产生细胞.
- 研究了IL-1β,巨细胞,MYD88和NOD2在调节IL-2的作用.
- 从克罗恩病患者的小肠组织中评估IL-2和Treg细胞水平.
主要成果:
- 3组先天性淋巴细胞 (ILC3) 是小肠中的IL-2的主要来源.
- ILC3s产生的IL-2由IL-1β诱导,而IL-1β是由巨细胞通过MYD88和NOD2感知微生物群产生的.
- 来自ILC3的IL-2对于维持Treg细胞,免疫平衡和口服耐受性至关重要.
- 在克罗恩病患者中观察到ILC3s减少IL-2的产生和较低的Treg细胞频率.
结论:
- 一个涉及微生物群,巨细胞,IL-1β和ILC3s的新途径调节小肠中的IL-2产生.
- ILC3衍生的IL-2在肠道免疫调节和口服耐受性中起着至关重要的作用.
- 在ILC3s中这种IL-2通路的失调可能会导致克罗恩病的发病.
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