病毒和细胞特异性HMGB1分泌和亚皮质透形成在腺病毒角膜炎
Amrita Saha1,2, Mohammad Mirazul Islam1,3, Rahul Kumar4
1Department of Ophthalmology, Massachusetts Eye and Ear, Harvard Medical School, Boston, Massachusetts, United States of America.
PLoS pathogens
|May 14, 2025
概括
人类腺病毒D (HAdV-D) 通过从角膜细胞分泌HMGB1引发流行角膜炎 (EKC). 这种蛋白质驱动白细胞透,解释了EKC中的角膜亚皮质透 (SEI).
科学领域:
- 眼科医生 眼科 眼科
- 病毒学 病毒学
- 免疫学 免疫学 免疫学
背景情况:
- 流行性角膜结膜炎 (EKC) 是由人类腺病毒 D 种 (HAdV-D) 引起的传染性眼睛感染,其特征是角膜亚皮质透 (SEI).
- 在EKC中SEI形成的确切机制尚不清楚.
- 高流动性组盒1蛋白 (HMGB1) 是感染期间释放的炎症警报蛋白.
研究的目的:
- 阐明HMGB1在HAdV-D感染期间角膜SEI的发病过程中的作用.
- 确定HMGB1分泌的特定机制及其对角膜组织的影响.
主要方法:
- 研究了HAdV-D感染的人类角膜上皮细胞的HMGB1分泌物.
- 利用细胞特异性测试和一种新的3D角膜培养模型.
- 检查了CRM1和LAMP1.1对HMGB1转移的调节.
- 评估了由HMGB1.1刺激的 stromal 细胞的化学激素表达.
主要成果:
- HAdV-D感染特别诱导人类角膜上皮细胞的HMGB1分泌,而不是其他细胞类型.
- HMGB1的分泌取决于乙化,并由CRM1和LAMP1.1调节.
- 细胞外的HMGB1刺激了主要的 stromal 细胞释放促炎性化学激素.
- 在3D角膜模型中,释放的HMGB1促进了白细胞透,解释了SEI的形成.
结论:
- 被HAdV-D感染的角膜上皮细胞分泌的HMGB1是驱动EKC中SEI的一个关键机制.
- 这个过程涉及受控的HMGB1转位和随后的角膜 stromal 细胞的炎症反应.
- 这些发现为EKC病原和潜在的治疗点提供了新的理解.
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