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IL-18驱动Bhlhe40介导的致病性Th17细胞反应,并加剧自身免疫性疾病的进展
Yuan Tang1,2, Yue Zhao1, Zixiang Chen3
1Department of Pathology, Shenzhen Institute of Research and Innovation, The University of Hong Kong, Hong Kong, China.
Cellular & molecular immunology
|October 14, 2025
概括
介素-18 (IL-18) 驱动致病性Th17 (pTh17) 细胞,恶化诸如Sjögren综合征和狼之类的自身免疫性疾病. 阻断IL-18显示出作为治疗这些疾病的新疗法的希望.
科学领域:
- 免疫学 免疫学 免疫学
- 自免疫性疾病 自免疫性疾病
- 分子生物学分子生物学
背景情况:
- 炎症性细胞因子的过度产生有助于免疫失调和组织损伤.
- 互白素-18 (IL-18) 在T细胞反应和自身免疫病原发生中的特定作用尚未完全理解.
研究的目的:
- 研究IL-18在T细胞分化中的作用及其对自身免疫性疾病的贡献.
- 探索IL-18作为自身免疫性疾病的潜在治疗点.
主要方法:
- 在Th17细胞中检测到IL-18受体α链 (IL-18Rα) 表达.
- 利用RNA测序来对IL-18诱导的致病性Th17 (pTh17) 细胞进行转录基因分析.
- 在患有原发性Sjögren综合征 (pSS) 和全身性红斑狼 (SLE) 的患者和小鼠模型中测量IL-18水平.
- 进行了IL-18诱导的pTh17细胞的采用转移和IL-18中和实验.
主要成果:
- IL-18 显著促进了 Th17 细胞分化和致病特征,包括 GM-CSF 生产.
- 由IL-18诱导的pTh17细胞表现出增加的糖解和促炎特征,通过Stat3-Bhlhe40信号传递进行介导.
- 增加的IL-18水平与pSS和SLE患者和小鼠模型中的疾病活性相关.
- 在实验性自身免疫模型中,IL-18阻断抑制了pTh17反应,改善了组织病理.
结论:
- 在自身免疫发育过程中,IL-18在驱动致病性Th17细胞反应方面起着至关重要的作用.
- IL-18 中和代表了对自身免疫性疾病的潜在治疗策略.
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