天生的淋巴细胞驱动了因特乐金-23-依赖的先天性肠道病理
Sofia Buonocore1, Philip P Ahern, Holm H Uhlig
1Sir William Dunn School of Pathology, University of Oxford, Oxford OX1 3RE, UK.
Nature
|April 16, 2010
概括
介素-23 (IL-23) 驱动先天性免疫细胞,特别是先天性淋巴细胞,产生炎症性细胞因子. 削弱这些细胞可以阻止结肠炎,从而揭示了炎症性肠道疾病的新治疗点.
科学领域:
- 免疫学 免疫学 免疫学
- 胃肠病学 胃肠病学
- 细胞生物学 细胞生物学
背景情况:
- 干白素-23 (IL-23) 涉及自身免疫和炎症性疾病,主要通过T-辅助17 (TH17) 细胞.
- IL-23也会影响天生的免疫细胞,导致T细胞独立性结肠炎,但下游途径尚不清楚.
研究的目的:
- 研究IL-23驱动的先天性肠炎的细胞和分子机制.
- 确定参与T细胞独立性大肠炎的新型细胞参与者和途径.
主要方法:
- 对结肠白细胞对IL-23刺激的反应中细胞因子 (IL-17,干扰素-) 的产生进行分析.
- 表达特定标记物的先天性淋巴细胞 (ILC) 的特征 (Thy1,SCA-1,ROR-合体,IL-23R).
- 在基因缺陷 (Rag-/-Rorc-/-) 和细胞枯竭 (Thy1+) 的小鼠模型中评估结肠炎的发展.
主要成果:
- 刺激IL-23诱导了IL-17和干扰素-的产生,由结肠中的特定的先天性淋巴细胞群体产生.
- 这些对IL-23敏感的ILCs,表达ROR-,在炎症的结肠中积累,对结肠炎的发展至关重要.
- 基因缺陷的ROR-马或耗尽的Thy1+ ILCs废除了急性和慢性先天性结肠炎.
结论:
- 一个独特的IL-23-响应的先天性淋巴细胞群介导肠道炎症.
- 这些发现确定了在炎症性肠病 (IBD) 中进行治疗干预的新型细胞点.
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