IL-21与抗TIGIT合作,在慢性HBV感染中恢复NK细胞功能
Libo Tang1, Quanrun Li1,2, Liang Chen1,3
1State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China.
Journal of medical virology
|October 10, 2023
概括
慢性乙型肝炎 (CHB) 感染会损害自然杀手 (NK) 细胞的功能. 介素-21 (IL-21) 和抗TIGIT疗法部分恢复NK细胞活性,促进HBV清除,提供新的免疫疗法策略.
科学领域:
- 免疫学 免疫学 免疫学
- 病毒学 病毒学
- 肝病学 肝病学是一种肝病学.
背景情况:
- 目前用于慢性乙型肝炎病毒 (HBV) 感染的治疗方法不足.
- 介素-21 (IL-21) 和检查点抑制剂是HBV的潜在免疫治疗选择.
- 通过IL-21和检查点抑制剂增强HBV清除的确切机制尚不清楚.
研究的目的:
- 调查IL-21和检查点抑制剂是否通过调节自然杀手 (NK) 细胞功能来促进HBV清除.
- 分析慢性HBV感染患者NK细胞的表型和功能变化.
主要方法:
- 测量了慢性HBV患者和健康对照中的mRNA和蛋白质水平的NK细胞表型和功能.
- 评估了telbivudine,IL-21和抗TIGIT在NK细胞功能上的作用,在体外和体内.
- 利用HBV感染的小鼠模型来评估IL-21和抗TIGIT的联合疗效.
主要成果:
- 慢性HBV感染显著改变NK细胞转录组,减少KLRK1,TIGIT,GZMA,PRF1,并增加CD69的表达.
- 来自HBV患者的NK细胞表现出NKG2D表达减少,TIGIT增加,以及干扰素- (IFN-γ) 和瘤亡因子-α (TNF-α) 生产受损,而telbivudine没有恢复这种情况.
- IL-21和抗TIGIT部分恢复了NK细胞功能;IL-21上调了激活受体并增强了NK细胞的细胞毒性和增殖,而抗TIGIT在CD56dim子集中特别增强了IFN-γ. 在小鼠中,IL-21对抗TIGIT介导的HBsAg清除至关重要.
结论:
- 慢性HBV感染导致NK细胞功能失调,其特征是特定的分子和功能障碍.
- IL-21和抗TIGIT代表有前途的治疗策略,可以部分恢复NK细胞抗病毒活性.
- IL-21和抗TIGIT的组合证明了增强HBV清除的新机制,突出了它们在免疫疗法设计中的潜力.
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