Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.
Stem Cell & Regenerative Medicine Center, Samsung Medical Center, Seoul, South Korea.
Front Cell Infect Microbiol. 2022 Aug 10;12:932373. doi: 10.3389/fcimb.2022.932373. eCollection 2022.
The intestinal microenvironment directly determines the human T-cell receptor (TCR) repertoire. Despite its extreme diversity, TCR repertoire analysis may provide a better understanding of the immune system in patients with inflammatory bowel disease.
To investigate TCR repertoires in the intestinal mucosa, RNA sequencing was performed for inflamed and non-inflamed intestinal mucosa samples obtained from 13 patients with Crohn's disease (CD) and healthy mucosa from nine non-IBD controls.
The gene expression frequency of the TCR repertoire showed a clear separation between inflamed mucosa of patients with CD and healthy mucosa of non-IBD controls in the hierarchical clustering heatmap. The richness of TCR repertoires measured by the Chao1 index did not show a significant difference among groups, whereas diversity measured by the D50 diversity index was decreased in the inflamed mucosa of CD patients. Rare/small TCR clonotypes occupied a large proportion of TCR repertoires in healthy mucosa of controls, whereas expanded clonotypes were common in inflamed mucosa of patients with CD. Segment usages of TRAV2, TRAV22, TRAV40, TRJ14, TRAJ51, TRBV1, TRBV21.1, and TRBJ1.5 were significantly decreased in CD patients. KEGG enrichment analysis identified the enrichment of several KEGG pathways, including inflammatory bowel disease ( = 0.0012), Th1 and Th2 cell differentiation ( = 0.0011), and intestinal immune network for IgA production ( = 0.0468).
The diversity of the TCR repertoire is reduced in inflamed mucosa of CD patients, which might contribute to intestinal inflammation.
肠道微环境直接决定了人类 T 细胞受体 (TCR) 库。尽管 TCR 库具有极高的多样性，但 TCR 库分析可能有助于更好地了解炎症性肠病患者的免疫系统。
为了研究肠道黏膜中的 TCR 库，对 13 例克罗恩病 (CD) 患者的炎症和非炎症肠道黏膜样本以及 9 例非 IBD 对照的健康黏膜样本进行了 RNA 测序。
在层次聚类热图中，CD 患者炎症黏膜和非 IBD 对照健康黏膜的 TCR 库基因表达频率明显分离。Chao1 指数衡量的 TCR 库丰富度在各组之间没有显著差异，而 D50 多样性指数衡量的多样性在 CD 患者的炎症黏膜中降低。在对照健康黏膜中，稀有/小 TCR 克隆型占据 TCR 库的很大比例，而在 CD 患者的炎症黏膜中，扩增的克隆型很常见。TRAV2、TRAV22、TRAV40、TRJ14、TRAJ51、TRBV1、TRBV21.1 和 TRBJ1.5 的 TRA 片段使用显著减少在 CD 患者中。KEGG 富集分析鉴定出几个 KEGG 途径的富集，包括炎症性肠病 (=0.0012)、Th1 和 Th2 细胞分化(=0.0011)和 IgA 产生的肠道免疫网络(=0.0468)。
CD 患者炎症黏膜中的 TCR 库多样性降低，这可能导致肠道炎症。
