CD27 co-stimulation increases the abundance of regulatory T cells and reduces atherosclerosis in hyperlipidaemic mice
CD27 co-stimulation increases the abundance of regulatory T cells and reduces atherosclerosis in hyperlipidaemic mice
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CD27 共刺激可增加高脂血症小鼠调节性 T 细胞的丰度并减少动脉粥样硬化
DOI：
10.1093/eurheartj/ehx517
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发表时间：
2017
影响因子：
39.3
通讯作者：
Gerdes N
中科院分区：
文献类型：
--
作者：
Winkels H;Meiler S;Lievens D;Engel D;Spitz C;Bürger C;Beckers L;Dandl A;Reim S;Ahmadsei M;Hartwig H;Holdt LM;Hristov M;Megens RTA;Schmitt MM;Biessen EA;Borst J;Faussner A;Weber C;Lutgens E;Gerdes N
目的共刺激受体CD27调节T细胞、B细胞和NK细胞的反应。多种T细胞亚群参与动脉粥样硬化形成。然而，CD27在动脉粥样硬化中的作用仍然unexplored.Methods和resultsHere，我们调查了骨髓来源的和系统性的CD27缺乏载脂蛋白E缺陷（Apoe −/−）小鼠动脉粥样硬化的早期和晚期阶段的影响。与接受Cd 27 +/+ Apoe −/−骨髓的小鼠相比，用Cd 27 −/− Apoe −/−骨髓重建并食用致动脉粥样硬化饮食的致死性辐照Apoe −/−小鼠显示出斑块大小和病变炎症显著增加。因此，喂食普通饲料的Cd27 −/− Apoe −/−小鼠在18周龄时表现出恶化的病变发展和增加的炎症。在动脉粥样硬化的更晚期（28周），两组之间的病变大小和表型没有差异。全身性和骨髓来源的CD27缺乏减少了血液、淋巴器官和主动脉中调节性T细胞（Treg）的丰度。当造血CD27缺乏时，其他免疫细胞的数量不受影响，而主动脉中炎性细胞因子基因（例如IL-1 β和IL-6）的表达增加。在体外，CD27缺乏小鼠的TCL4显示出与野生型对照组相似的抑制能力，并且向CCL19和CCL21的迁移相同。然而，胸腺细胞Cd27 −/− TdR在体内经历了增加的凋亡，并表达了较少的增殖标记物。重建ofCd27 −/− Apoe −/−小鼠与Cd27 +/+ Apoe −/− Tclasses逆转了动脉粥样硬化的增加。ConclusionWe表明，CD27共刺激增加Tclasses的数量和限制病变发展和炎症实验性动脉粥样硬化，特别是在疾病的早期阶段。因此，我们的研究表明，促进CD27功能可能会减轻动脉粥样硬化。
AimsThe co-stimulatory receptor CD27 modulates responses of T cells, B cells, and NK cells. Various T cell subsets participate in atherogenesis. However, the role of CD27 in atherosclerosis remains unexplored.Methods and resultsHere we investigated the effect of bone marrow-derived and systemic CD27 deficiency in Apolipoprotein E-deficient (Apoe−/−) mice in early and advanced stages of atherosclerosis. Lethally-irradiated Apoe−/−mice reconstituted with Cd27−/−Apoe−/−bone marrow and consuming an atherogenic diet displayed a markedly increased plaque size and lesional inflammation compared to mice receiving Cd27+/+Apoe−/−bone marrow. Accordingly, chow diet-fed Cd27−/−Apoe−/−mice showed exacerbated lesion development and increased inflammation at the age of 18 weeks. At a more advanced stage of atherosclerosis (28 weeks), lesion size and phenotype did not differ between the two groups. Systemic and bone marrow-derived CD27 deficiency reduced the abundance of regulatory T cells (Treg) in blood, lymphoid organs, and the aorta. Numbers of other immune cells were not affected while expression of inflammatory cytokine genes (e.g. IL-1βand IL-6) was increased in the aorta when haematopoietic CD27 was lacking.In vitro, Tregs of CD27-deficient mice showed similar suppressive capacity compared with their wild-type controls and migrated equally towards CCL19 and CCL21. However, thymicCd27−/−Tregs underwent increased apoptosis and expressed fewer markers of proliferationin vivo. Reconstitution ofCd27−/−Apoe−/−mice withCd27+/+Apoe−/−Tregs reversed the increase in atherosclerosis.ConclusionWe demonstrate that CD27 co-stimulation increases the number of Tregs and limits lesion development and inflammation in experimental atherosclerosis, particularly during early stages of disease. Thus, our study suggests that promotion of CD27 function may mitigate atherosclerosis.
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影响因子：
29.7
作者：
Josefowicz SZ;Lu LF;Rudensky AY
通讯作者：
Rudensky AY
影响因子：
15.9
作者：
Peperzak, Victor;Xiao, Yanling;Borst, Jannie
通讯作者：
Borst, Jannie
DOI：
10.1146/annurev-pathol-020712-163936
发表时间：
2014
期刊：
Annual review of pathology
影响因子：
--
作者：
Witztum JL;Lichtman AH
通讯作者：
Lichtman AH
影响因子：
6.7
作者：
Gerdes, Norbert;Zirlik, Andreas
通讯作者：
Zirlik, Andreas
影响因子：
4.4
作者：
Pen, Joeri J.;De Keersmaecker, Brenda;Aerts, Joeri L.
通讯作者：
Aerts, Joeri L.