在败血症期间,HOTAIRM1控制了S100A9蛋白质酸化在髓衍生的抑制细胞中
Isatou Bah1, Dima Youssef1, Zhi Q Yao1,2
1Department of Internal Medicine, Infectious Disease and Immunity, East Tennessee State University College of Medicine, Johnson City, TN 37614, USA.
Journal of clinical & cellular immunology
|December 12, 2024
概括
Hotairm1,一个长非编码RNA,限制了S100A9蛋白质的酸化,在败血症期间促进其在髓质衍生抑制细胞中的核定位. 准Hotairm1可能会减少免疫抑制并改善败血症的生存率.
科学领域:
- 免疫学 免疫学 免疫学
- 分子生物学分子生物学
- 遗传学 是一个遗传学.
背景情况:
- 败血症涉及复杂的免疫失调,其特征是明显的急性和慢性阶段.
- 在急性败血症中,S100A9蛋白从酸化的细胞溶液形式转变为慢性败血症中的非酸化的核形式.
- 骨髓系衍生抑制细胞 (MDSCs) 在败血症诱导的免疫抑制中发挥着关键作用.
研究的目的:
- 调查长非编码RNAHotairm1在调节S100A9局部化和酸化在MDSCs在败血症期间的作用.
- 为了确定Hotairm1对S100A9.9的p38 MAPK酸化的影响.
- 探索针对Hotairm1的治疗潜力,以调节MDSC功能并改善败血症的结果.
主要方法:
- 从败血症小鼠和人类的MDSC中对Hotairm1的击败.
- 感染早期败血症Gr1+CD11b+细胞以增加Hotairm1水平.
- 评估-S100A9蛋白水平和IL-10的产生.
- 对S100A9核定位的分析.
主要成果:
- 在晚期败血症中,Hotairm1 knockdown MDSCs增加了-S100A9水平.
- 在早期败血症细胞中增加Hotairm1减少了-S100A9.9.
- 霍塔尔姆1通过p38 MAPK限制了S100A9的酸化.
- 在晚期败血症中,Hotairm1 knockdown MDSCs 降低了IL-10的产生.
结论:
- Hotairm1通过抑制p38 MAPK.它的酸化来促进非酸化S100A9的核转移.
- 调节Hotairm1水平会影响S100A9酸化状态和MDSC中的IL-10产生.
- 针对Hotairm1提出了一个潜在的策略,以减少MDSC扩张,缓解免疫抑制,并改善败血症的生存率.
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