Distinct Injury Responsive Regulatory T Cells Identified by Multi-Dimensional Phenotyping.
Distinct Injury Responsive Regulatory T Cells Identified by Multi-Dimensional Phenotyping.
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DOI：
10.3389/fimmu.2022.833100
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发表时间：
2022
影响因子：
7.3
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中科院分区：
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CD 4+调节性T细胞（TCRs）在不同类型的损伤中活化和扩增，这表明它们在控制对组织和细胞损伤的免疫反应中起着关键作用。该项目使用多维谱分析技术来全面表征小鼠中的损伤响应性TdR。我们发现，CD 44高TcB在对损伤的反应中扩增，并且与CD 44低TcB相比具有高度抑制性。T细胞受体（TCR）库分析显示，CD 44 highTreg群体经历TCRαβ克隆扩增以及TCR CDR 3多样性增加。批量RNA测序和单细胞RNA测序与配对TCR克隆型分析确定了CD 44高和CD 44低TCR之间的独特差异，以及TCR克隆型扩增后TCR中基因的特异性上调。对RNA测序数据的分子功能的基因本体分析确定趋化因子受体和细胞分裂是CD 44高T细胞与CD 44低T细胞中最丰富的功能术语。对来自损伤和未损伤小鼠的Tcells的质谱（CyTOF）分析证实了这些基因在CD 44 high Tcells上的蛋白表达，损伤诱导的Helios、Galectin-3和PYCARD表达增加。总之，这些数据表明，损伤触发了高度抑制性CD 44 high Treg群体的扩增，该群体在转录和表型上不同于CD 44 low Treg，表明它们积极参与控制对损伤和组织损伤的免疫应答。
CD4+ regulatory T cells (Tregs) activate and expand in response to different types of injuries, suggesting that they play a critical role in controlling the immune response to tissue and cell damage. This project used multi-dimensional profiling techniques to comprehensively characterize injury responsive Tregs in mice. We show that CD44high Tregs expand in response to injury and were highly suppressive when compared to CD44low Tregs. T cell receptor (TCR) repertoire analysis revealed that the CD44high Treg population undergo TCRαβ clonal expansion as well as increased TCR CDR3 diversity. Bulk RNA sequencing and single-cell RNA sequencing with paired TCR clonotype analysis identified unique differences between CD44high and CD44low Tregs and specific upregulation of genes in Tregs with expanded TCR clonotypes. Gene ontology analysis for molecular function of RNA sequencing data identified chemokine receptors and cell division as the most enriched functional terms in CD44high Tregs versus CD44low Tregs. Mass cytometry (CyTOF) analysis of Tregs from injured and uninjured mice verified protein expression of these genes on CD44high Tregs, with injury-induced increases in Helios, Galectin-3 and PYCARD expression. Taken together, these data indicate that injury triggers the expansion of a highly suppressive CD44high Treg population that is transcriptionally and phenotypically distinct from CD44low Tregs suggesting that they actively participate in controlling immune responses to injury and tissue damage.