Olofsson Peder S, Steinberg Benjamin E, Sobbi Roozbeh, Cox Maureen A, Ahmed Mohamed N, Oswald Michaela, Szekeres Ferenc, Hanes William M, Introini Andrea, Liu Shu Fang, Holodick Nichol E, Rothstein Thomas L, Lövdahl Cecilia, Chavan Sangeeta S, Yang Huan, Pavlov Valentin A, Broliden Kristina, Andersson Ulf, Diamond Betty, Miller Edmund J, Arner Anders, Gregersen Peter K, Backx Peter H, Mak Tak W, Tracey Kevin J
Center for Bioelectronic Medicine, Department of Medicine, Center for Molecular Medicine, Solna, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
Laboratory of Biomedical Science, The Feinstein Institute for Medical Research, Manhasset, New York, USA.
Nat Biotechnol. 2016 Oct;34(10):1066-1071. doi: 10.1038/nbt.3663. Epub 2016 Sep 12.
Blood pressure regulation is known to be maintained by a neuro-endocrine circuit, but whether immune cells contribute to blood pressure homeostasis has not been determined. We previously showed that CD4 T lymphocytes that express choline acetyltransferase (ChAT), which catalyzes the synthesis of the vasorelaxant acetylcholine, relay neural signals. Here we show that these CD4CD44CD62L T helper cells by gene expression are a distinct T-cell population defined by ChAT (CD4 T). Mice lacking ChAT expression in CD4 cells have elevated arterial blood pressure, compared to littermate controls. Jurkat T cells overexpressing ChAT (JT) decreased blood pressure when infused into mice. Co-incubation of JT and endothelial cells increased endothelial cell levels of phosphorylated endothelial nitric oxide synthase, and of nitrates and nitrites in conditioned media, indicating increased release of the potent vasorelaxant nitric oxide. The isolation and characterization of CD4 T cells will enable analysis of the role of these cells in hypotension and hypertension, and may suggest novel therapeutic strategies by targeting cell-mediated vasorelaxation.
已知血压调节由神经内分泌回路维持，但免疫细胞是否有助于血压稳态尚未确定。我们之前表明，表达胆碱乙酰转移酶（ChAT）的CD4 T淋巴细胞可传递神经信号，ChAT催化血管舒张剂乙酰胆碱的合成。在此我们表明，通过基因表达，这些CD4CD44CD62L T辅助细胞是由ChAT定义的独特T细胞群体（CD4 T）。与同窝对照相比，CD4细胞中缺乏ChAT表达的小鼠动脉血压升高。将过表达ChAT的Jurkat T细胞（JT）注入小鼠后可降低血压。JT与内皮细胞共同孵育可增加条件培养基中磷酸化内皮型一氧化氮合酶以及硝酸盐和亚硝酸盐的内皮细胞水平，表明强效血管舒张剂一氧化氮的释放增加。CD4 T细胞的分离和表征将有助于分析这些细胞在低血压和高血压中的作用，并可能通过靶向细胞介导的血管舒张提出新的治疗策略。
