在严重的酒精相关性肝炎中,细胞毒性T细胞和NK细胞的功能下降
Adam Kim1, Christina K Cajigas-Du Ross1, Jaividhya Dasarathy2
1Northern Ohio Alcohol Center, Department of Inflammation and Immunity, Cleveland Clinic, Cleveland, OH 44195, USA.
概括
患有严重酒精相关性肝炎 (sAH) 的患者表现出功能障碍的NK细胞,影响他们对抗感染的能力. 这项研究揭示了SAH中细胞毒性细胞功能受损,增加了感染风险.
科学领域:
- 免疫学 免疫学 免疫学
- 肝病学 肝病学是一种肝病学.
- 细胞生物学 细胞生物学
背景情况:
- 代谢性肝病如酒精性和非酒精性脂肪性肝病 (ALD/NAFLD) 引起炎症和易受感染.
- 患有严重酒精相关性肝炎 (sAH) 的患者在类固醇治疗期间特别容易感染感染.
- 细胞毒性NK细胞和CD8T细胞对于清除感染细胞至关重要,但它们的功能在SAH中受损.
研究的目的:
- 调查SAH患者感染易感性增加背后的免疫机制.
- 了解为什么NK细胞在SAH患者中功能障碍.
- 为了确定SAH患者和健康对照者之间的细胞毒性细胞中的分子差异.
主要方法:
- 在外周血液单核细胞 (PBMCs) 上使用单细胞RNA测序 (scRNA-seq) 的探索性研究.
- 进行了多面板细胞内流细胞计,对来自sAH患者和健康对照 (HC) 的PBMC进行了检查.
主要成果:
- scRNA-seq在NK和CD8T细胞中确定了下调受体,用于识别SAH患者的激活单细胞.
- 一个关键的细胞毒性基因 - - 粒素素在sAH患者的NK细胞和CD8T细胞中显著下调.
- 来自SAH患者的NK细胞显示了细胞毒性颗粒基因 (granulysin,perforin,granzymes) 的协调表达丧失和细胞分解性颗粒蛋白表达减少,表明细胞毒性功能受损.
结论:
- 患有SAH的患者在PBMC中表现出细胞毒性细胞功能丧失.
- 这种功能障碍可能会损害与其他免疫细胞 (如单细胞) 的通信,并降低消除感染细胞的能力.
- 这些发现表明,一种机制有助于在sAH患者中观察到的感染风险增加.
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