在患有活跃结核病的患者中,促剂甲基化和PD-L1的增加表达
Yen-Han Tseng1,2, Sheng-Wei Pan1,2,3, Jhong-Ru Huang2,4
1Department of Chest Medicine, Taipei Veterans General Hospital Taipei, 112 Taiwan.
Microbial cell (Graz, Austria)
|July 31, 2024
概括
在活跃结核病 (TB) 患者中,编程细胞死亡蛋白1联体1 (PD-L1) 表达率升高,与治疗结果有关. 在Mycobacterium结核病感染期间,DNA甲基化会影响巨细胞中的PD-L1水平.
科学领域:
- 免疫学 免疫学 免疫学
- 分子生物学分子生物学
- 传染性疾病 传染性疾病
背景情况:
- PD-1/PD-L1通路调节T细胞活性,并与Mycobacterium结核病 (MTB) 感染病理生理学有关.
- 已知DNA甲基化可以控制癌症中的PD-L1表达,但其在MTB感染期间对巨细胞的作用尚不清楚.
研究的目的:
- 调查DNA甲基化在活性结核病 (TB) 期间巨细胞中调节PD-L1表达中的作用.
- 检查结核病患者中PD-L1表达,甲基化相关基因,疾病严重程度和治疗结果之间的相关性.
主要方法:
- 活跃结核病患者和非结核病对照患者的未来招募.
- 在PBMC中分析PD-L1和甲基化相关基因表达.
- 对于PD-L1促进物甲基化的双硫酸盐序列.
- 肺组织和巨细胞系上的免疫组织化学和免疫光.
- 在巨细胞中操纵DNA甲基转移酶 (DNMTs) 和TET酶.
主要成果:
- 活跃结核病患者的PD-L1,DNMT3b,TET1,TET2和DNMT1表达率高,低于对照组.
- PD-L1和TET-1表达与较差的治疗结果相关 (延迟的培养转化).
- 在结核病患者的巨细胞和MTB刺激的细胞系中共定位PD-L1和TET-1.
- DNMT抑制增加了PD-L1,而TET-1敲击降低了巨细胞中的PD-L1表达.
结论:
- 在活跃的结核病中,PD-L1表达上调,与治疗结果有关.
- 涉及DNMTs和TET酶的DNA甲基化机制在MTB感染期间在巨细胞中调节PD-L1表达方面发挥着重要作用.
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