染色质活性可确定T细胞状态

作者: 小柯机器人 来源: 科学网 更新时间:2019年09月24日 点击数:

2019-09-24

英国威康桑格研究所Gosia Trynka课题组近日发现GWAS基因座上的染色质活性确定了驱动复杂免疫疾病的T细胞状态。相关论文在线发表在2019年9月23日的《自然—遗传学》杂志上。

研究人员用13种细胞因子刺激了T细胞和巨噬细胞,并分析了活跃和开放染色质区域。T细胞活化引起主要的染色质重塑,而细胞因子的存在则微调了变化的幅度。研究人员开发了一种统计方法,以解决染色质全貌中的细微变化,从而确定不同细胞状态的SNP富集。研究人员的结果表明,免疫疾病相关变体在记忆CD4 阳性T细胞的早期激活而非晚期激活中的起作用,而不同细胞因子的差异不大。

此外,与炎症性肠病相关的变体富含1型辅助性T(TH1)细胞,而与阿尔茨海默症相关的变体则富含不同的巨噬细胞状态。这些结果体现了对T细胞和巨噬细胞活化状态的全面分析中与免疫疾病相关变体的深入分析。

研究人员表示,T细胞和巨噬细胞的活跃染色质区域富含免疫疾病相关变体。但是,这些变体是否在特定细胞状态下起作用尚不清楚。

附:英文原文

Title: Chromatin activity at GWAS loci identifies T cell states driving complex immune diseases

Author: Blagoje Soskic, Eddie Cano-Gamez, Deborah J. Smyth, Wendy C. Rowan, Nikolina Nakic, Jorge Esparza-Gordillo, Lara Bossini-Castillo, David F. Tough, Christopher G. C. Larminie, Paola G. Bronson, David Will, Gosia Trynka

Issue&Volume: 2019-09-23

Abstract: 

Immune-disease-associated variants are enriched in active chromatin regions of T cells and macrophages. However, whether these variants function in specific cell states is unknown. Here we stimulated T cells and macrophages in the presence of 13 cytokines and profiled active and open chromatin regions. T cell activation induced major chromatin remodeling, while the presence of cytokines fine-tuned the magnitude of changes. We developed a statistical method that accounts for subtle changes in the chromatin landscape to identify SNP enrichment across cell states. Our results point towards the role of immune-disease-associated variants in early rather than late activation of memory CD4+ T cells, with modest differences across cytokines. Furthermore, variants associated with inflammatory bowel disease are enriched in type 1 T helper (TH1) cells, whereas variants associated with Alzheimer’s disease are enriched in different macrophage cell states. Our results represent an in-depth analysis of immune-disease-associated variants across a comprehensive panel of activation states of T cells and macrophages.

DOI: 10.1038/s41588-019-0493-9

Source: https://www.nature.com/articles/s41588-019-0493-9

 

期刊信息

Nature Genetics:《自然—遗传学》,创刊于1992年。隶属于施普林格·自然出版集团,最新IF:25.455
官方网址:https://www.nature.com/ng/

 

棋牌游戏平台_首页