Differential expression profile of gluten-specific T cells identified by single-cell RNA-seq

Gluten-specific CD4+ T cells drive the pathogenesis of celiac disease and circulating gluten-specific T cells can be identified by staining with HLA-DQ:gluten tetramers. In this first single-cell RNA-seq study of tetramer-sorted T cells from untreated celiac disease patients blood, we found that gluten-specific T cells showed distinct transcriptomic profiles consistent with activated effector memory T cells that shared features with Th1 and follicular helper T cells. Compared to non-specific cells, gluten-specific T cells showed differential expression of several genes involved in T-cell receptor signaling, translational processes, apoptosis, fatty acid transport, and redox potentials. Many of the gluten-specific T cells studied shared T-cell receptor with each other, indicating that circulating gluten-specific T cells belong to a limited number of clones. Moreover, the transcriptional profiles of cells that shared the same clonal origin were transcriptionally more similar compared with between clonally unrelated gluten-specific cells.EGA study EGAS00001005517

谷蛋白特异性CD4+ T细胞（gluten-specific CD4+ T cells）介导乳糜泻（celiac disease）的发病机制，循环中的谷蛋白特异性T细胞可通过HLA-DQ：谷蛋白四聚体（HLA-DQ:gluten tetramers）染色实现鉴定。本研究首次采用单细胞RNA测序（single-cell RNA-seq）技术，对未接受治疗的乳糜泻患者外周血中经四聚体（tetramer）分选的T细胞开展分析，结果显示谷蛋白特异性T细胞具备独特的转录组谱（transcriptomic profiles），其特征与活化效应记忆T细胞（activated effector memory T cells）高度吻合，且同时兼具辅助性T细胞1（Th1）与滤泡辅助性T细胞（follicular helper T cells）的相关特性。与非特异性细胞相比，谷蛋白特异性T细胞在多个参与T细胞受体信号通路（T-cell receptor signaling）、翻译过程、细胞凋亡（apoptosis）、脂肪酸转运及氧化还原电位调控的基因中呈现显著差异表达。本研究分析的大量谷蛋白特异性T细胞彼此共享T细胞受体（T-cell receptor），提示循环中的谷蛋白特异性T细胞仅归属于有限的数个克隆谱系。此外，拥有相同克隆起源（clonal origin）的细胞，其转录谱相较于克隆无关的谷蛋白特异性T细胞，转录特征更为相似。欧洲基因组学档案（European Genome-phenome Archive，EGA）研究 EGAS00001005517