氨酸受体CD44通过调节中性粒细胞迁移来驱动COVID-19的严重程度
Duncan J Hart1, Md Jashim Uddin1, Rebecca J Dodd2,3
1Department of Microbiology, Immunology and Cancer Biology, University of Virginia School of Medicine, Charlottesville, Virginia, USA.
bioRxiv : the preprint server for biology
|November 24, 2025
概括
用抗体阻断氨酸 (HA) 受体CD44,改善了SARS-CoV-2感染小鼠的生存率和减少了肺炎. 这表明向HA-CD44相互作用可能是重症COVID-19的新疗法.
科学领域:
- 免疫学 免疫学 免疫学
- 病毒学 病毒学
- 细胞外矩阵生物学 细胞外矩阵生物学
背景情况:
- 作为全球卫生紧急情况的COVID-19需要新的治疗策略.
- 细胞外矩阵 (ECM) 在宿主-病原体相互作用中的作用,特别是在COVID-19中,是研究不足的.
- 肺部的氨酸 (HA) 沉积与严重的COVID-19结果相关,其受体CD44对免疫细胞功能至关重要.
研究的目的:
- 调查COVID-19中HA沉积增加通过CD44介导的免疫细胞透加剧肺病理的假设.
- 在SARS-CoV-2感染的小鼠模型中评估阻断HA-CD44相互作用的治疗潜力.
主要方法:
- 在小鼠模型中发现SARS-CoV-2感染.
- 用两种抗CD44单克隆抗体的组合治疗.
- 评估存活率,体重减轻,临床分数,支气管洗液中的细胞因子/化学因子水平,通过流动细胞计数计数的中性粒细胞数量,以及通过免疫光检测的HA-免疫细胞局部化.
主要成果:
- 抗CD44抗体治疗显著改善了感染小鼠的生存率,减轻了体重减轻,并降低了感染小鼠的临床分数.
- 治疗导致肺部关键炎症性细胞因子和化学因子的水平降低.
- 流细胞计和免疫光检测显示,治疗小鼠的肺部中性粒细胞透率降低,HA与免疫细胞 (CD45) 的同位化减少.
结论:
- 在SARS-CoV-2感染的小鼠模型中,阻断氨酸 (HA) -CD44与单克隆抗体的相互作用为生存带来了好处,并减少了肺病理.
- 准HA-CD44通路是一种有前途的治疗策略,可以缓解炎症反应,并改善COVID-19等肺部感染的结果.
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