来自质细胞的神经调节剂控制3型先天性淋巴细胞和肠道防御
Sales Ibiza1, Bethania García-Cassani1, Hélder Ribeiro1
1Instituto de Medicina Molecular, Faculdade de Medicina de Lisboa, Av. Prof. Egas Moniz, Edifício Egas Moniz, 1649-028 Lisboa, Portugal.
Nature
|July 14, 2016
概括
质细胞和第三组先天性淋巴细胞 (ILC3) 形成了调节肠道防御的单元. 神经营养不良因素控制了先天的IN-22 (IL-22) 生产,影响了炎症和感染敏感性.
科学领域:
- 免疫学
- 神经科学
- 胃肠病学
背景情况:
- 第三组先天性淋巴细胞 (ILC3) 是粘膜免疫的关键调节者.
- ILC3感知和响应其微观环境的机制尚未完全理解.
研究的目的:
- 研究质细胞和神经营养因子在ILC3介导的肠道防御中的作用.
- 阐明涉及ILC3质细胞通信的信号通路.
主要方法:
- 在ILC3和质细胞中具有向基因缺失的小鼠模型 (Ret,Myd88).
- 对免疫细胞种群,细胞因子 (IL-22) 生产,上皮反应性和肠道微生物群的分析.
- 包括p38 MAPK/ERK-AKT和STAT3在内的信号级联的调查.
主要成果:
- 肠道ILC3表达神经食受体RET;ILC3中的Ret切除损害IL-22的产生,上皮防御,并增加对炎症和感染的易感性.
- 质细胞与ILC3相邻,产生通过p38 MAPK/ERK-AKT和STAT3调节IL-22的神经营养因子.
- 特定于质细胞的Myd88删除会损害IL-22的产生,并加剧肠道炎症和感染.
结论:
- 一个由神经营养因子控制的新型质ILC3上皮细胞单元, 控制肠道防御.
- 质细胞作为中央调节器,通过神经营养因素整合神经元和免疫信号.
- 这一发现突出了调节粘膜屏障内生免疫力的新途径.
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