SIKs 调节 HDAC7 稳定和细胞因子召回在晚期T细胞效应因子分化中
Rachel S Helms1, Alberto Marin-Gonzalez2,3,4, Chirag H Patel1,5
1The Bloomberg-Kimmel Institute for Cancer Immunotherapy, Sidney-Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, MD.
Journal of immunology (Baltimore, Md. : 1950)
|November 10, 2023
概括
研究人员发现,肝激酶B1 (LKB1) 激活盐可诱导激酶,这些激酶在表观遗传上控制T细胞细胞因子回忆. 抑制这种途径可以增强效应T细胞的功能,从而提供新的治疗点.
科学领域:
- 免疫学 免疫学 免疫学
- 细胞生物学 细胞生物学
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
背景情况:
- T细胞分化对免疫反应至关重要,并且在疾病中可能受到失调.
- 了解效应器功能维护是治疗策略的关键.
研究的目的:
- 为了确定T细胞效应因子功能的新型调节剂.
- 研究肝激酶B1 (LKB1) 和盐诱导激酶 (SIK) 在T细胞分化中的作用.
主要方法:
- 使用激酶抑制剂BioE-1197来探测T细胞信号通路.
- 在 CD8+ 和 Th1 效应细胞中检查了表观遗传修饰,包括基因素乙化 (H3K27Ac).
- 评估细胞因子基因表达和在再刺激后的召回潜力.
主要成果:
- 由LKB1介导的SIK激活在表观遗传上调节了细胞因子召回潜力.
- SIK的激活导致了基因素脱乙酶7 (HDAC7) 的稳定,并增加了核水平.
- HDAC7稳定降低了H3K27Ac在细胞因子基因位点,损害了再刺激诱导的细胞因子产生.
结论:
- 一个涉及LKB1,SIK和HDAC7的新途径控制了效应T细胞中细胞因子生产的表观遗传记忆.
- 在分化过程中抑制这种途径可以增强T细胞细胞因子召回潜力.
- 这确定了调节T细胞介导免疫的新目标.
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