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巨细胞基因表达的极端个体间变异与对炎症性肠病的遗传易感性之间的关系
Claire L O'Brien1,2, Kim M Summers3, Natalia M Martin2
1Centre for Research in Therapeutics Solutions, Faculty of Science and Technology, University of Canberra, Canberra, ACT, Australia.
巨细胞中的基因表达变异,特别是对脂多糖 (LPS) 的反应,与炎症性肠病 (IBD) 易感性有关. 个人基因失调,而不是整体网络变化,似乎对IBD遗传风险至关重要.
科学领域:
- 免疫学 免疫学 免疫学
- 遗传学 是一个遗传学.
- 胃肠病学 胃肠病学
背景情况:
- 居民肠道巨细胞与血液单细胞有区别,这一过程由巨细胞殖民地刺激因子受体 (CSF1R) 调节.
- 全基因组关联研究 (GWAS) 表明,改变的巨细胞分化和微生物反应有助于炎症性肠病 (IBD) 的易感性.
研究的目的:
- 研究IBD患者和健康个体的单细胞衍生巨细胞 (MDM) 的转录组变异.
- 识别与IBD易感性相关的基因表达模式.
主要方法:
- 从IBD家族和健康对照组中分析MDM的转录组变异.
- 转录网络分析和对基因表达的相关性分析,以响应脂多糖 (LPS).
- 调查单核酸变异 (SNV) 基因型与基因表达的关联.
主要成果:
- 在受影响和未受影响的个体之间没有发现基底或LPS诱导的基因表达的显著整体或相互差异.
- 观察到基底和LPS诱导基因表达的显著个体间变异 (高达100倍).
- 与HLA基因型相关的HLA相关转录的极端变异.
- 早期IL1B和IFNB1表达的变异与本地SNV基因型有关,并预测了下游目标基因的表达.
结论:
- 巨细胞适应肠道环境的基因特异性失调与IBD的遗传易感性有关.
- 影响巨细胞反应途径的个体遗传变异可能会导致IBD的发病.
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