胰岛素受体协调脏的抗菌防御
Laura Schwartz1,2, Aaron Simoni1, Pearlly Yan3,4
1The Kidney and Urinary Tract Center, Abigail Wexner Research Institute at Nationwide Children's, Columbus, OH 43205.
概括
在糖尿病中,脏收集管细胞中的胰岛素受体 (IR) 信号受损会损害对尿路感染 (UTI) 的防御能力. 恢复IR功能可以增强对细菌感染的免疫力.
科学领域:
- 腎臟病學 (nephrology) 是一種醫學專業.
- 免疫学 免疫学 免疫学
- 内分泌学 在内分泌学.
背景情况:
- 糖尿病增加了对尿路感染 (UTI) 的易感性.
- 脏采集管细胞,特别是间隔细胞 (ICs),在尿路感染防御中发挥作用.
- 在IC中失调的胰岛素受体 (IR) 信号与增加的尿路感染风险有关.
研究的目的:
- 调查IR删除在ICs对抗菌防御对尿病原菌大肠杆菌的影响.
- 检查IC中的IR删除如何影响邻近主细胞 (PC) 的免疫反应.
- 阐明IR在编排收集管道抗菌反应和细胞间通信中的作用.
主要方法:
- 从野生类型和特定于IC的IR淘汰小鼠中进行ICs和PCs的转录形状分析.
- 利用小鼠和人类细胞培养来研究红外线信号和免疫反应.
- 研究激活转录因子4 (ATF4) 和NFkB通路在IR介导免疫中的作用.
主要成果:
- 在IC中IR删除抑制了综合应激反应和先天免疫力.
- 细胞中的失调的红外信号破坏了ATF4的激活,导致NFkB的激活受损,并增加了对感染的易感性.
- 抑制NFkB通路进一步增加了感染,并减少了抗微生物的表达.
- 糖尿病模型显示红外表达减少,应激反应受损,以及免疫力减弱的收集管细胞.
结论:
- 红外线信号对于脏收集管细胞中编排抗菌防御至关重要.
- 损坏的红外功能会破坏集成的应激反应和IC和PC之间的通信,导致糖尿病中尿路感染的易感性.
- 这些发现突显了糖尿病患者中IR功能,免疫力和尿路感染风险之间的转化联系.
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