de Jong Maaike J M, Depuydt Marie A C, Schaftenaar Frank H, Liu Kun, Maters David, Wezel Anouk, Smeets Harm J, Kuiper Johan, Bot Ilze, van Gisbergen Klaas, Slütter Bram
Division of Biotherapeutics, Leiden Academic Centre for Drug Research, Leiden University, the Netherlands (M.J.M.d.J., M.A.C.D., F.H.S., K.L., D.M., J.K., I.B., B.S.).
Department of Surgery, Haaglanden Medical Center, The Hague, the Netherlands (A.W., H.J.S.).
Arterioscler Thromb Vasc Biol. 2024 Jun;44(6):1318-1329. doi: 10.1161/ATVBAHA.123.320511. Epub 2024 Apr 18.
Tissue resident memory T (T) cells are a T-cell subset that resides at the site of prior antigen recognition to protect the body against reoccurring encounters. Besides their protective function, T cells have also been implicated in inflammatory disorders. T cells are characterized by the expression of CD69 and transcription factors Hobit (homolog of Blimp-1 [B lymphocyte-induced maturation protein 1] in T cells) and Blimp-1. As the majority of T cells in the arterial intima expresses CD69, T cells may contribute to the pathogenesis of atherosclerosis as well. Here, we aimed to assess the presence and potential role of T cells in atherosclerosis.
To identify T cells in human atherosclerotic lesions, a single-cell RNA-sequencing data set was interrogated, and T-cell phenotypes were compared with that of integrated predefined T cells. The presence and phenotype of T in atherosclerotic lesions was corroborated using a mouse model that enabled tracking of Hobit-expressing T cells. To explore the function of T cells during atherogenesis, RAG1 (recombination activating gene 1 deficient) LDLr (low-density lipoprotein receptor knockout) mice received a bone marrow transplant from HobitBlimp-1 mice, which exhibit abrogated T cell formation, whereafter the mice were fed a Western-type diet for 10 weeks.
Human atherosclerotic lesions contained T cells that exhibited a T cell-associated gene signature. Moreover, a fraction of these T cells clustered together with predefined T cells upon integration. The presence of Hobit-expressing T cells in the atherosclerotic lesion was confirmed in mice. These lesion-derived T cells were characterized by the expression of CD69 and CD49α. Moreover, we demonstrated that this small T-cell subset significantly affects lesion composition, by reducing the amount of intralesional macrophages and increasing collagen content.
T cells, characterized by the expression of CD69 and CD49α, constitute a minor population in atherosclerotic lesions and are associated with increased lesion stability in a Hobit and Blimp-1 knockout mouse model.
组织驻留记忆T（Trm）细胞是一种T细胞亚群，驻留在先前抗原识别的部位，以保护机体免受再次接触抗原的影响。除了其保护功能外，Trm细胞还与炎症性疾病有关。Trm细胞的特征是表达CD69以及转录因子Hobit（T细胞中B淋巴细胞诱导成熟蛋白1 [Blimp-1]的同源物）和Blimp-1。由于动脉内膜中的大多数Trm细胞表达CD69，因此Trm细胞可能也参与动脉粥样硬化的发病机制。在此，我们旨在评估Trm细胞在动脉粥样硬化中的存在情况及其潜在作用。
为了鉴定人类动脉粥样硬化病变中的Trm细胞，我们查阅了单细胞RNA测序数据集，并将Trm细胞表型与整合的预定义Trm细胞进行比较。使用能够追踪表达Hobit的Trm细胞的小鼠模型，证实了动脉粥样硬化病变中Trm细胞的存在及其表型。为了探究Trm细胞在动脉粥样硬化发生过程中的功能，RAG1（重组激活基因1缺陷）LDLr（低密度脂蛋白受体敲除）小鼠接受了来自HobitBlimp-1小鼠的骨髓移植，这些小鼠表现出Trm细胞形成受阻，然后给这些小鼠喂食西式饮食10周。
人类动脉粥样硬化病变中含有表现出Trm细胞相关基因特征的Trm细胞。此外，在整合后，这些Trm细胞中的一部分与预定义的Trm细胞聚集在一起。在小鼠中证实了动脉粥样硬化病变中存在表达Hobit的Trm细胞。这些源自病变的Trm细胞的特征是表达CD69和CD49α。此外，我们证明，这个小的Trm细胞亚群通过减少病变内巨噬细胞的数量和增加胶原蛋白含量，显著影响病变组成。
以表达CD69和CD49α为特征的Trm细胞在动脉粥样硬化病变中占少数，并在Hobit和Blimp-1基因敲除小鼠模型中与病变稳定性增加相关。
