介素-17直接刺激瘤透Tregs,以防止癌症的发展
William C Theune1, Ju Chen1,2, Eileen Victoria Theune1
1Department of Immunology, School of Medicine, University of Connecticut Health Center, Farmington, CT, United States.
Frontiers in immunology
|July 1, 2024
概括
互白素-17 (IL-17) 直接向调节性T细胞 (Tregs) 发出信号,促进它们的功能和控制炎症. 这一发现揭示了一个负反循环,对于控制结肠直肠癌 (CRC) 癌症发展至关重要.
科学领域:
- 免疫学 免疫学 免疫学
- 分子生物学分子生物学
- 在瘤学瘤学.
背景情况:
- 介素-17 (IL-17) 细胞因子家族对病原体耐药性至关重要,但也与自身免疫和瘤进展有关.
- IL-17对调节性T细胞 (Tregs) 的直接信号传递以前尚未确定,这阻碍了对其双重作用的理解.
研究的目的:
- 研究IL-17信号传递对调控性T细胞 (Tregs) 的直接影响.
- 阐明IL-17-Treg相互作用在结直肠癌 (CRC) 发展背景下的作用.
主要方法:
- 在Tregs (Il17ra^ΔTreg小鼠) 中产生了IL-17受体A (IL-17RA) 的条件淘汰.
- 通过收养将骨髓细胞转移到偶发性结直肠癌的小鼠模型中.
- 在从小鼠和人类结直肠瘤中纯化的Tregs上利用单细胞和散装RNA测序.
主要成果:
- IL-17受体A (IL-17RA) 在小鼠介质淋巴结和结肠瘤中的Tregs中表达.
- 在Tregs中切除IL-17RA导致Th17细胞增加,并加剧瘤发育.
- 瘤透Tregs显示一个独特的基因特征支持激活,成熟和抑制,部分由直接IL-17信号介导.
- 瘤Tregs中的IL-17RA损失导致RNA剪接减少和关键RNA结合蛋白的下调.
结论:
- 直接向Tregs发送IL-17信号,促进它们的成熟和功能.
- 这种IL-17-Treg信号通路作为负反循环来调节结直肠癌 (CRC) 中促进癌症的炎症.
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