CD4+ T cells From Children With Active Juvenile Idiopathic Arthritis Show Altered Chromatin Features Associated With Transcriptional Abnormalities (RNA-seq)

We used a multi-omics approach in an attempt to identify mechanisms driving the transcriptional abnormalities in peripheral blood CD4+ T cells of children with active JIA. We demonstrate that active JIA is associated with distinct alterations in CD4+ T cell chromatin, as assessed by ATAC-seq studies. However, 3D chromatin architecture, assessed by HiChIP and simultaneous mapping of CTCF anchors of chromatin loops, reveals that normal 3D chromatin architecture is largely preserved in JIA CD4+ T cells. However, overlapping CTCF binding, ATACseq, and RNAseq data with known JIA genetic risk loci demonstrated the presence of genetic influences on the observed transcriptional abnormalities and identified candidate target genes. These studies demonstrate the utility of multi-omics approaches for unraveling some of the most vexing questions regarding the pathobiology of autoimmune diseases. The distinct alterations of the gene expression in CD4+ T cell was assessed by RNA-seq.

本研究采用多组学方法，旨在明确活动性幼年特发性关节炎（Juvenile Idiopathic Arthritis, JIA）患儿外周血CD4+ T细胞中转录异常的潜在机制。本研究通过ATAC-seq分析证实，活动性JIA与CD4+ T细胞染色质的显著改变密切相关。然而，通过HiChIP技术以及染色质环CTCF锚点同时定位分析评估的三维染色质结构却显示，JIA患儿CD4+ T细胞的正常三维染色质结构基本得以保留。不过，将CTCF结合数据、ATAC-seq数据与RNA-seq数据与已知的JIA遗传风险位点进行整合分析后发现，观测到的转录异常存在遗传影响因素，并鉴定出了候选靶基因。上述研究证实了多组学方法在解析自身免疫性疾病病理生物学领域诸多棘手问题方面的应用价值。本研究通过RNA-seq技术检测了CD4+ T细胞中基因表达的显著改变。