CD1d-Dependent Natural Killer T Cells Mediate Hypertension and Vascular Injury Through Interleukin-17A.
CD1d-Dependent Natural Killer T Cells Mediate Hypertension and Vascular Injury Through Interleukin-17A.
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cd1依赖性自然杀伤T细胞通过白细胞介素- 17a介导高血压和血管损伤。
DOI：
10.1161/jaha.122.029179
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发表时间：
2023-07-04
影响因子：
5.4
通讯作者：
Wang, Hong-Xia
中科院分区：
文献类型：
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作者：
Xiao, Xue;Hou, Cui-Liu;Zhang, Yun-Long;Yang, Hui;Wang, Xiao-Xiao;Wang, Hong-Xia
不同的T淋巴细胞亚群，包括CD 1d依赖性自然杀伤T（NKT）细胞，在高血压中发挥不同的作用，突出了识别关键免疫细胞对其治疗的重要性。本研究旨在确定CD 1d依赖性NKT细胞对高血压和血管损伤的未知作用。在雄性CD 1d敲除（CD 1dko）、野生型和过继骨髓转移小鼠中，通过血管紧张素II（Ang II）或脱氧皮质酮醋酸盐诱导高血压模型。通过尾套系统和无线电遥测测量血压。通过组织学研究或主动脉环测定评估血管损伤。通过流式细胞术、定量真实的时间聚合酶链反应或ELISA检测炎症。结果显示，血管紧张素Ⅱ输注可显著降低小鼠主动脉CD 1d表达和NKT细胞数量。CD 1dko小鼠表现出恶化的血压升高，血管损伤，和炎症反应诱导的血管紧张素II或脱氧皮质酮醋酸盐。然而，这些作用在用NKT细胞特异性激活剂处理的野生型小鼠中显著逆转。将CD 1dko骨髓细胞连续转移至野生型小鼠也显著恶化了Ang II诱导的反应。在机制上，CD 1dko增加了Ang II诱导的白细胞介素-6的产生，并激活了信号转导和转录激活因子3和孤儿核受体γ，随后诱导白细胞介素-17 A的产生。在CD 1dko小鼠中，中和白细胞介素-17A可部分逆转Ang II诱导的高血压和血管损伤。此外，与血压正常的个体（n=87）相比，高血压患者（n=57）血液中的NKT细胞水平较低。这些发现揭示了CD 1d依赖性NKT细胞在高血压和血管损伤中的未知作用，表明NKT细胞活化可能是高血压的一个有希望的治疗靶点。
Different T‐lymphocyte subsets, including CD1d‐dependent natural killer T (NKT) cells, play distinct roles in hypertension, highlighting the importance of identifying key immune cells for its treatment. This study aimed to determine the unknown effects of CD1d‐dependent NKT cells on hypertension and vascular injury. Hypertension models were induced in male CD1d knockout (CD1dko), wild‐type, and adoptive bone marrow transfer mice by angiotensin II (Ang II) or deoxycorticosterone acetate salt. Blood pressure was measured by the tail‐cuff system and radiotelemetry. Vascular injury was assessed by histologic studies or aortic ring assay. Inflammation was detected by flow cytometry, quantitative real‐time polymerase chain reaction, or ELISA. Results showed that Ang II infusion significantly reduced CD1d expression and NKT cell numbers in the aorta of mice. CD1dko mice exhibited worsened blood pressure elevation, vascular injury, and inflammatory response induced by Ang II or deoxycorticosterone acetate salt. However, these effects were markedly reversed in wild‐type mice treated with NKT cell–specific activator. Adoptive transfer of CD1dko bone marrow cells to wild‐type mice also significantly worsened Ang II–induced responses. Mechanistically, CD1dko increased Ang II–induced interleukin‐6 production and activated signal transducer and activator of transcription 3 and orphan nuclear receptor γ, subsequently inducing interleukin‐17A production. Neutralizing interleukin‐17A partially reversed Ang II–induced hypertension and vascular injury in CD1dko mice. In addition, levels of NKT cells were lower in the blood of patients with hypertension (n=57) compared with normotensive individuals (n=87). These findings reveal a previously unknown role for CD1d‐dependent NKT cells in hypertension and vascular injury, indicating that NKT cell activation could be a promising therapeutic target for hypertension.