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在中枢神经系统炎症期间, IL-23-STAT4 途径对于经典树突细胞的炎症前作用是必需的

Nada S Alakhras^1,2, Wenwu Zhang², Nicolas Barros³

¹Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN 46202.

Proceedings of the National Academy of Sciences of the United States of America

|August 1, 2024

概括

在树突细胞 (DCs) 中的信号转换器和转录4 (STAT4) 激活器对于多发性硬化症等炎症性疾病至关重要. 这项研究确定了DC中驱动疾病的关键IL-23-STAT4通路.

科学领域:

免疫学免疫学免疫学
细胞生物学细胞生物学
神经科学是一个神经科学.

背景情况:

细胞因子信号传递对于树突细胞 (DC) 的发育和功能至关重要.
信号转换器和转录激活器4 (STAT4) 调解对 IL-12 和 IL-23 等促炎细胞因子的反应.
STAT4在自身免疫性疾病中发挥作用,包括实验性自身免疫性脑膜炎 (EAE),这是多发性硬化症 (MS) 的模型.

研究的目的:

研究STAT4在成熟树突细胞内在功能中的作用.
确定DC中STAT4信号是否对于启动T细胞反应和EAE中中枢神经系统炎症至关重要.

主要方法:

在EAE模型中使用了缺乏STAT4在CD11c表达细胞中的条件突变小鼠.
采用从野生类型和STAT4缺乏的小鼠获得的骨髓衍生DC的采用转移实验.
进行单细胞RNA测序 (RNA-seq) 来识别DC子集中的STAT4依赖基因表达.

主要成果:

在DC中STAT4缺陷显著降低了EAE中的T细胞原始化和中枢神经系统炎症.
采用野生型DC的转移恢复了STAT4缺乏的接受者的EAE易受性,而不是转移STAT4或IL-23R缺乏的DC.
RNA-seq揭示了DCs中的STAT4依赖基因特征,与MS患者DCs中发现的相关.

结论:

树突细胞中的IL-23-STAT4信号通路对于炎症性疾病期间的DC功能至关重要.
对DC固有的STAT4对于驱动T细胞反应和EAE病变发生至关重要.
这一途径代表了MS和其他炎症状况的潜在治疗标.

关键词:

欧洲电子商务管理局 (EEAE)在STAT4中,我们使用了STAT4.细胞因子细胞因子树突细胞是一种树突细胞.

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