天生的淋巴细胞调节CD4+T细胞对肠道共生细菌的反应
Matthew R Hepworth1, Laurel A Monticelli, Thomas C Fung
1Division of Gastroenterology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
Nature
|May 24, 2013
概括
天生的淋巴细胞 (ILC) 通过与T细胞相互作用来调节肠道免疫力. 这些ILCs限制了对肠道细菌的有害反应,保持肠道平衡,防止炎症.
科学领域:
- 免疫学 免疫学 免疫学
- 胃肠病学 胃肠病学
背景情况:
- 天生的淋巴细胞 (ILC) 对肠道屏障完整性至关重要.
- 失调的ILC与炎症性肠病有关.
- 之前对ILC的研究往往缺乏适应性免疫,限制了对其在复杂免疫环境中的作用的理解.
研究的目的:
- 为了研究ILCs在完整的适应性免疫系统中的功能.
- 确定ILCs如何影响自适应性免疫细胞反应,特别是对共生细菌的影响.
主要方法:
- 利用基因和抗体介导的枯竭来准与视网膜酸受体相关的孤儿受体-γt-阳性 (RORγt(+)) ILCs.
- 进行了全基因组的转录分析和功能分析.
- 研究了主要组织相容性复合物II类 (MHCII) 在ILCs上的作用.
主要成果:
- 失去RORγt (((+) ILCs导致适应性免疫对抗开始性细菌和全身炎症的调节失调.
- RORγt(+) ILCs表达MHCII和存在的抗原,但限制,而不是促进CD4(+) T细胞反应.
- 缺乏MHCII的ILCs导致无法控制的T细胞反应和自发的肠道炎症.
结论:
- RORγt(+) ILCs通过通过MHCII-依赖的相互作用来限制病理适应性免疫反应对共生细菌来维持肠道平衡.
- ILCs在肠道内的免疫调节中发挥着关键作用,独立于IL-17A,IL-22或IL-23.
- 这项研究揭示了在适应性免疫的背景下,ILCs通过免疫调节的新机制.
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