CD161(+) Tconv and CD161(+) Treg Share a Transcriptional and Functional Phenotype despite Limited Overlap in TCRβ Repertoire.
CD161(+) Tconv and CD161(+) Treg Share a Transcriptional and Functional Phenotype despite Limited Overlap in TCRβ Repertoire.
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DOI：
10.3389/fimmu.2017.00103
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发表时间：
2017
影响因子：
7.3
通讯作者：
Wedderburn LR
中科院分区：
文献类型：
--
作者：
Duurland CL;Brown CC;O'Shaughnessy RF;Wedderburn LR
人类调节性T细胞（Treg）在免疫调节中很重要，但也可以在特定环境中显示可塑性。CD161是一种凝集素样受体，其表达鉴定了效应子样Treg群体。在这里，我们确定了CD161+ Treg与CD161+常规T细胞（Tconv）的关系。转录谱鉴定了CD161+ Tconv和CD161+ Treg之间的共享转录特征，其与辅助性T细胞（Th）1和Th17细胞以及组织归巢（包括肠道归巢受体的高表达）相关。视黄酸（RA）暴露后，CD161+ T细胞比CD161− T细胞更富集CCR9+和整合素α4+β7+细胞。此外，CD161+ Tconv和CD161+ Treg在自身免疫性关节炎的炎症部位富集，并且来自炎症部位的CD161+和CD161− Treg在体外具有抑制性。来自自身免疫性关节炎部位的CD161+ T细胞表现出减少的肠道归巢表型和对RA的钝化反应，表明RA在肠道或外周部位而不是在滑膜炎症期间预先印迹。来自血液的CD161+和CD161− Tconv和Treg的TCRβ库显示出有限的重叠，而来自炎症部位的CD161+和CD161− Tconv以及CD161+和CD161− Treg之间存在明显的重叠，这表明炎症环境可能会改变CD161水平，可能有助于疾病的发病机制。
Human regulatory T cells (Treg) are important in immune regulation, but can also show plasticity in specific settings. CD161 is a lectin-like receptor and its expression identifies an effector-like Treg population. Here, we determined how CD161+ Treg relate to CD161+ conventional T cells (Tconv). Transcriptional profiling identified a shared transcriptional signature between CD161+ Tconv and CD161+ Treg, which is associated with T helper (Th)1 and Th17 cells, and tissue homing, including high expression of gut-homing receptors. Upon retinoic acid (RA) exposure, CD161+ T cells were more enriched for CCR9+ and integrin α4+β7+ cells than CD161− T cells. In addition, CD161+ Tconv and CD161+ Treg were enriched at the inflamed site in autoimmune arthritis, and both CD161+ and CD161− Treg from the inflamed site were suppressive in vitro. CD161+ T cells from the site of autoimmune arthritis showed a diminished gut-homing phenotype and blunted response to RA suggesting prior imprinting by RA in the gut or at peripheral sites rather than during synovial inflammation. TCRβ repertoires of CD161+ and CD161− Tconv and Treg from blood showed limited overlap whereas there was clear overlap between CD161+ and CD161− Tconv, and CD161+ and CD161− Treg from the inflamed site suggesting that the inflamed environment may alter CD161 levels, potentially contributing to disease pathogenesis.