介质蛋白-17 控制受损表皮的低氧适应
Piotr Konieczny1, Yue Xing1, Ikjot Sidhu1,2
1Department of Pathology, New York University Langone Health, New York, NY 10016, USA.
Science (New York, N.Y.)
|June 16, 2022
概括
伤害引起的缺氧本身不会激活受损表皮的HIF1α. 相反,来自 γδ T 细胞的互白素-17A (IL-17A) 激活HIF1α,驱动上皮细胞修复所必需的糖解.
科学领域:
- 免疫学
- 细胞生物学
- 分子生物学
背景情况:
- 哺乳动物细胞激活低氧诱导的转录因子 (HIF),以在低氧条件下生存.
- 受伤引起的缺氧不足以激活受损的上皮细胞中的HIF1α.
研究的目的:
- 研究在上皮细胞修复过程中激活HIF1α的信号通路和免疫细胞参与.
- 阐明IL-17A-HIF1α轴在表皮细胞适应低氧压力的作用.
主要方法:
- 多模式单细胞和空间转录组学分析.
- 涉及基因操纵和药物抑制的功能研究.
- 包括AKT,ERK1/2和mTOR在内的信号通路的分析.
主要成果:
- 与视网膜酸相关的孤儿受体 γt+ (RORγt+) γδ T 细胞衍生IL-17A对于受损表皮的HIF1α激活是必要的和足够的.
- IL-17A通过AKT和ERK1/ 2信号激活HIF1α,从而导致mTOR激活.
- IL-17A-HIF1α轴促进伤口前表皮质的糖分分解,这对修复至关重要.
- 干扰IL-17RC,HIF1α或糖解会影响上皮的愈合.
结论:
- 由 γδ T 细胞产生的 IL- 17A 是上皮细胞修复过程中 HIF1α 激活的关键启动剂.
- IL-17A-HIF1α通路结合了炎症,代谢和迁移过程,以有效地治疗上皮质.
- 免疫细胞衍生信号在组织修复过程中对细胞适应低氧压力起到关键作用.
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