I型IFN诱导在γδ内皮质淋巴细胞中的TCR依赖和独立的抗菌反应
Matthew A Fischer1,2, Luo Jia1, Karen L Edelblum1,2
1Center for Immunity and Inflammation, Department of Pathology, Immunology and Laboratory Medicine, Rutgers New Jersey Medical School, Newark, NJ.
一种类型的干扰素 (IFN) 与低T细胞受体 (TCR) 激活相结合,会诱导玛三角 intraepithelial 淋巴细胞 (γδ IELs) 中的IFN-γ产生. 这条通路对宿主防御病原体至关重要.
科学领域:
- 免疫学 免疫学 免疫学
- 细胞生物学 细胞生物学
- 传染性疾病 传染性疾病
背景情况:
- 表达T细胞受体马三角体 (TCRγδ) 的内皮细胞 (IEL) 对肠道免疫非常重要.
- I型干扰子 (IFN) 在调节 γδ IEL 效应器功能的作用尚未完全理解.
- γδ IELs弥合了先天性和适应性免疫力,这表明它在各种免疫反应中发挥了作用.
研究的目的:
- 调查I型IFN信号如何影响γδ IEL功能.
- 阐明I型IFN介导的γδ IEL激活背后的分子机制.
- 为了确定I型IFN和TCR信号在γδ IEL反应中的in vivo相关性.
主要方法:
- ex vivo 培养小鼠的 γδ IEL.
- 用I型IFN和不同水平的TCR激活的刺激.
- 对IFN-γ的产生和分子信号通路 (NFAT,JNK,STAT4) 的分析.
- 在体内实验评估γδ IEL反应.
主要成果:
- 单独的I型IFN并没有诱导ex vivo的γδIEL中IFN-γ的产生.
- 低水平的TCR激活与I型IFN协同作用,通过NFAT,JNK和STAT促进IFN-γ的产生4.
- 第一种类型的IFN快速上调抗病毒基因,独立于TCR信号传递.
- 在体内,I型IFN诱导的IFN-γ产生需要绕过近端TCR信号事件.
结论:
- γδ IELs对独立于TCRγδ信号的I型IFN产生快速的抗菌反应.
- 由 γδ IEL 发生的依赖于 TCR 的 IFN-γ 生产在涉及 I 型 IFN 和特定信号通路的允许条件下发生.
- 这些发现凸显了gδ IELs在对病原体的宿主防御中的双重机制.
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