SO2通过JAK1,2/STAT3信号通路激活Th17细胞
Maoyu Ye1, Guohao Deng1, Qian Liu2
1Department of Otorhinolaryngology-Head and Neck Surgery, Third Xiangya Hospital, Central South University, China.
International immunopharmacology
|October 1, 2024
概括
二氧化硫 (SO2) 暴露会通过促进Th1,Th2和Th17细胞使过敏性鼻炎 (AR) 炎症恶化. JAK/STAT路径抑制剂鲁克索利提尼布有效降低了SO2诱导的Th17炎症,提供了一个潜在的AR治疗点.
科学领域:
- 免疫学 免疫学 免疫学
- 环境健康 环境健康
- 分子生物学分子生物学
背景情况:
- 过敏性鼻炎 (AR) 涉及复杂的免疫反应.
- 二氧化硫 (SO2) 是一种已知的环境污染物,具有潜在的免疫调节作用.
- 辅助T细胞 (Th) 的作用,特别是Th1,Th2和Th17,以及JAK/STAT信号通路在AR病变发生过程中的作用需要进一步阐明.
研究的目的:
- 研究SO2暴露对AR患者Th1,Th2和Th17细胞群的影响.
- 探索 Janus 激酶 (JAK) 1,2/信号转换器和转录激活器 (STAT) 3 信号通路在 SO2 诱导的免疫反应中的参与.
- 为了确定AR治疗的潜在治疗点.
主要方法:
- 来自AR患者和健康对照者的外周血液单核细胞 (PBMC) 被培养并用SO2衍生物刺激.
- 使用流细胞计分析Th细胞子集 (Th1,Th2,Th17,Treg) 和细胞因子表达.
- 使用定量实时PCR (qRT-PCR) 和西部斑分析来评估关键细胞因子和信号分子 (JAK1,JAK2,STAT3,RORγt) 的基因和蛋白质表达.
- 使用JAK抑制剂鲁克索利替尼 (Ruxolitinib) 来检测JAK/STAT通路的作用.
主要成果:
- 在AR患者和健康个体中,SO2刺激可提高Th1,Th2和Th17细胞和相关细胞因子的调节.
- 观察到IL-17A,RORγt和IL-6的水平升高,以及SO2暴露后Jurkat细胞中JAK1,JAK2,STAT3和RORγt的表达增加.
- 卢克索利提尼布治疗抑制了JAK/STAT通路,显著降低了Th17细胞数量,IL-17A水平和RORγt表达,表明SO2对Th17分化的影响是由JAK/STAT信号传导的.
结论:
- 暴露于SO2会加剧AR中的Th1/Th2/Th17炎症,并且可以诱导健康个体的Th1和Th17炎症.
- 在SO2诱导的Th17细胞分化和炎症中,JAK/STAT信号通路起着至关重要的作用.
- 正如Ruxolitinib所证明的那样,抑制JAK/STAT通路是一种有前途的治疗策略,用于控制与SO2相关的过敏炎症.
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