表观遗传读者蛋白SP140调节树突细胞活化,成熟和宽容性潜力
Mohammed Ghiboub1,2, Matthew Bell2, Dovile Sinkeviciute2
1Tytgat Institute for Liver and Intestinal Research, Amsterdam Gastroenterology, Endocrinology Metabolism, Amsterdam University Medical Centers, Location AMC, University of Amsterdam, 1105 BK Amsterdam, The Netherlands.
Current issues in molecular biology
|May 26, 2023
概括
使用GSK761抑制SP140蛋白减少了树突细胞 (DC) 中的炎症反应. 这表明,针对SP140可能有助于通过促进免疫耐受性来治疗自身免疫和炎症性疾病.
科学领域:
- 免疫学 免疫学 免疫学
- 分子生物学分子生物学
- 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:
- SP140是一种表观遗传读者蛋白,涉及免疫细胞.
- 在SP140的遗传变异与自身免疫和炎症性疾病有关.
- 在巨细胞中抑制SP140可降低炎症性细胞因子表达.
研究的目的:
- 调查SP140抑制剂GSK761对人类树突细胞 (DC) 分化和成熟的影响.
- 评估SP140抑制对细胞因子产生和DCs对T细胞刺激的影响.
- 探索针对SP140治疗免疫媒介疾病的潜力.
主要方法:
- 人类DCs被用GSK761或SP140 siRNA治疗.
- 脂聚糖 (LPS) 用于刺激DCs.
- 分析了细胞因子,共刺激分子和成熟标记物的表达.
- 在DC刺激后评估T细胞激活和表型变化.
主要成果:
- 在DCs中,LPS增加了SP140表达和招募到促炎性细胞因子基因促进体.
- 在DC中,GSK761治疗减少了LPS诱导的TNF,IL-6和IL-1β表达.
- GSK761抑制了DC成熟,减少了CD83,CD80,CD86和CD1b的表达.
- 由GSK761治疗的DCs刺激的T细胞显示TBX21/RORA减少和FOXP3表达增加,表明调节性T细胞生成.
结论:
- 抑制SP140会影响DC成熟和促炎性细胞因子的产生.
- 准SP140促进DCs中的耐受性特性.
- 抑制SP140为自身免疫和炎症性疾病提供了潜在的治疗策略.
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