腺脱氨酶活性中的性别差异与SARS-CoV-2先天免疫力的差异有关
Priyanka Saminathan1, Ian T Mathews1,2, Ahmad Alimadadi1,3
1Center for Sex Differences in the Immune System, La Jolla Institute for Immunology, La Jolla, CA 92037, USA.
iScience
|May 9, 2025
概括
由于较低的腺脱氨酶 (ADA) 活性,女性表现出更强的抗病毒免疫力,导致人体内源逆转录病毒 (hERV) 和干扰素刺激基因 (ISG) 表达的增加. 这种性别差异会影响免疫反应,特别是在COVID-19等呼吸道感染中.
科学领域:
- 免疫学 免疫学 免疫学
- 遗传学 是一个遗传学.
- 病毒学 病毒学
背景情况:
- 雌性具有增强的I型干扰素生产和抗病毒免疫力,但潜在的机制尚不清楚.
- 以前的研究将低氨酸脱氨酶 (ADA) 活性与人类内源逆转录病毒元素 (hERV) 的扰乱甲基化沉默联系起来,随后刺激干扰素刺激基因 (ISG) 并启动抗病毒免疫力.
研究的目的:
- 调查抗病毒免疫力基于性别差异背后的机制.
- 探索腺脱氨酶 (ADA) 活性和人类内源逆转录病毒 (hERV) 元素在性别特异性免疫反应中的作用.
主要方法:
- 在女性和男性受试者中对ADA活性,hERV和ISG表达的比较分析.
- 来自COVID-19患者的呼吸细胞的单细胞RNA测序.
- 免疫标记物,单细胞群和临床结果之间的相关性分析.
主要成果:
- 与男性相比,女性的ADA活性较低,与肺组织中较高的hERV和ISG表达相关.
- 在ADA2中,性别差异与独特的单细胞群有关.
- COVID-19患者数据显示,hERV-ISG签名中存在女性偏差,IL-18与性别特定的ADA2调节有关.
- 在男性中,较高的ADA活性与呼吸道内源性抗病毒免疫抑制相关.
结论:
- 女性较低的ADA活性有助于增强hERV和ISG的表达,从而产生强大的抗病毒免疫反应.
- 这些基于性别的免疫差异,受到ADA2和单细胞特征的影响,可能会影响COVID-19等呼吸道感染的易感性和结果.
- 男性的ADA活性升高与抗病毒免疫力下降有关,这可能解释了COVID-19的不良结果.
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