CD161+ Tconv and Treg share transcriptome and display a migratory phenotype which is modified at the inflamed site. Homo sapiens

Regulatory T cells (Treg) are a cornerstone of immune regulation. Recent evidence indicates that human Treg show plasticity in specific settings. A subpopulation of Treg expressing CD161, a marker associated with T helper (Th)17 cells, have T effector -like characteristics and are enriched at sites of autoimmune inflammation. Here we used RNAseq to confirm the effector-like signature of CD161+ Treg and demonstrated a shared transcriptional signature between CD161+ Treg and CD161+ conventional T cells (Tconv). Pathway analysis suggested that CD161+ T cells have a migratory phenotype, expressing high levels of CCR9 and integrin α4β7, markers associated with gut homing. In response to all-trans retinoic acid, CD161+ T cells expressed higher levels of CCR9 and integrin α4β7 than CD161- T cells. Our data suggest that blood CD161+ T cells may have adopted gut homing properties upon retinoic acid exposure. In contrast to their peripheral counterparts, CD161+ T cells from the site of autoimmune arthritis have a diminished gut homing phenotype and blunted response to retinoic acid. In health, the TCRβ repertoires of CD161+ and CD161- T cells showed limited overlap whereas there is clear overlap in T cell clones from synovial fluid of autoimmune arthritis patients. We therefore propose that CD161+ and CD161- T cells are largely distinct populations in the healthy immune system but that the inflamed site creates an environment where CD161 levels in T cells can be altered, potentially contributing to disease pathogenesis. Overall design: Transcriptional profilling of CD161+ and CD161- Tconv, and CD161+ and CD161- Tconv from blood of healthy adult controls. The raw files provided are BAM files, and the two associated raw files are merged into one BAM file for each sample. Note: Sample 2 CD161+ Treg was excluded due to low cDNA yield

调节性T细胞（Regulatory T cells, Treg）是免疫调控的核心基石。近期研究证据表明，人类Treg在特定环境中可表现出可塑性。表达CD161的Treg亚群——该标志物与辅助性T（T helper, Th）17细胞相关——具有类似效应T细胞的特征，且在自身免疫炎症部位富集。本研究通过RNA测序（RNAseq）验证了CD161+ Treg的效应样转录特征，并证实CD161+ Treg与CD161+ 常规T细胞（conventional T cells, Tconv）共享一套转录特征。通路分析显示，CD161+ T细胞具有迁移表型，高表达CCR9与整合素α4β7——这两种标志物均与肠道归巢相关。在全反式维甲酸（all-trans retinoic acid）刺激下，CD161+ T细胞的CCR9与整合素α4β7表达水平显著高于CD161- T细胞。本研究数据表明，血液中的CD161+ T细胞在暴露于维甲酸后可获得肠道归巢特性。与外周来源的CD161+ T细胞不同，自身免疫性关节炎病灶来源的CD161+ T细胞的肠道归巢表型减弱，且对维甲酸的应答也被削弱。在健康状态下，CD161+与CD161- T细胞的TCRβ受体库重叠有限，但自身免疫性关节炎患者滑液中的T细胞克隆则存在明显重叠。因此我们提出，在健康免疫系统中，CD161+与CD161- T细胞大体上属于两个独立的细胞群，但炎症部位会营造出可改变T细胞CD161表达水平的微环境，这可能参与疾病的发病机制。

总体实验设计：对健康成年对照血液中的CD161+与CD161- 常规T细胞（Tconv）以及CD161+与CD161- 调节性T细胞（Treg）进行转录组分析。本研究提供的原始文件为BAM文件，每个样本的两份关联原始文件将合并为一个BAM文件。

注意事项：样本2的CD161+ Treg因cDNA产量过低被排除