安德روج因在流感病毒感染期间保护ILC2S免受功能抑制
bioRxiv : the preprint server for biology
|February 3, 2025
概括
女性流感A病毒感染显示,由于IFNGR较高,免疫细胞被抑制. 男性的雌激素受体活性通过调节IFNGR-STAT1信号来维持免疫细胞的功能.
科学领域:
- 免疫学 免疫学 免疫学
- 病毒学 病毒学
- 内分泌学 在内分泌学.
背景情况:
- 生物性别影响流感A病毒 (IAV) 发病率,部分是通过免疫反应.
- 女性表现出更强的干扰素中心免疫力,但性激素受体在免疫细胞中的作用尚不清楚.
- 肺部居住的2组先天性淋巴细胞 (ILC2s) 表达雄激素受体 (AR) 并对IAV感染修复至关重要,但可以通过1型细胞因子抑制.
研究的目的:
- 为了研究肺部ILC2功能抑制IAV感染期间的性别差异.
- 阐明雄激素受体 (AR) 和干扰素信号在基于性别的ILC2调节中的作用.
主要方法:
- 在亚致命性IAV感染期间,从雄性和雌性小鼠获得的肺ILC2s的比较分析.
- 评估ILC2的扩散,细胞因子的产生,GATA3和IL-33R的表达.
- 转录组分析,IFNγ刺激测定和STAT1/AR缺陷模型.
主要成果:
- 与男性相比,女性ILC2s表现出减弱的增殖,减少的IL-5/amphiregulin生产,以及较低的GATA3/IL-33R表达.
- 在IFNγ刺激后,女性ILC2s表现出IFNGR表达的升高和更高的-STAT1水平.
- 淋巴细胞受限的STAT1缺陷逆转了女性ILC2的IAV诱导的抑制,而AR缺陷或雄激素损失抑制了男性ILC2s.
结论:
- 雌性ILC2s的内在因素有助于它们在IAV感染期间的功能抑制.
- 男性的雄激素受体 (AR) 活性调节IFNGR-STAT1信号传递,保持ILC2功能.
- 这些发现凸显了AR在病毒感染期间基于性别调节免疫细胞反应中的作用.
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