CD1d依赖的自然杀伤T细胞在高血压发生发展中的作用及机制

批准号:
81970349
项目类别:
面上项目
资助金额:
55.0 万元
负责人:
王红霞
依托单位:
学科分类:
血压调节异常与高血压病
结题年份:
2023
批准年份:
2019
项目状态:
已结题
项目参与者:
王红霞
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中文摘要
不同T细胞亚群在高血压中具有不同的作用,但高血压时T淋巴细胞亚群分化和激活的分子机制并不清楚。CD1d依赖的自然杀伤T细胞(NKT),可同时调节先天和获得性免疫,参与T淋巴细胞亚群的分化,但在高血压发病中的意义并不清楚。我们前期发现血管紧张素Ⅱ(Ang Ⅱ)灌注可明显下调呈递糖脂类抗原的CD1d分子表达;应用使NKT细胞失活的CD1d分子敲除小鼠加重Ang Ⅱ灌注引起的血压升高,而NKT细胞特异性激动剂可明显拮抗Ang Ⅱ处理引起的改变。本项目将在基因敲除、骨髓移植及激动剂处理的小鼠以及体外细胞共培养体系中,采用经典的Ang Ⅱ灌注和DOCA-盐处理方法复制高血压模型,阐明CD1d表达下调的分子机制;明确CD1d依赖的NKT细胞对血管功能、血管壁厚度、炎症反应和纤维化的影响,从而导致血压升高及血管重塑发生的机制,据此证明CD1d分子下调,引起NKT细胞激活减少,导致血压升高的科学假说。
英文摘要
Different T lymphocyte subsets play different roles in hypertension, but the molecular mechanism of regulating T lymphocyte subsets differentiation and activation in hypertension is not clear. CD1d-dependent natural killer T cells (NKT) can regulate both innate and acquired immunity and participate in the differentiation of T lymphocyte subsets. However, the significance of CD1d-dependent NKT in the pathogenesis of hypertension is unclear. Our previous studies found that angiotensin II (Ang II) infusion could significantly down-regulate the expression of CD1d molecule- presenting glycolipid antigen. The use of CD1d molecule knockout mice which can inactivate NKT cells aggravated the elevation of blood pressure induced by Ang II perfusion, and NKT cell specific agonists could significantly antagonize the changes induced by Ang II treatment. This project will elucidate the molecular of down-regulation of CD1d expression in mice with gene knockout, bone marrow transplantation, agonist treatment and in vitro cell co-culture system by classical the hypertensive model induced by Ang II perfusion and DOCA-salt treatment. To clarify the mechanism of blood pressure elevation and vascular remodeling by observing the effects of CD1d-dependent NKT cells on vascular function, vascular wall thickness, inflammatory response and fibrosis. In view of the above, the project will prove the hypothesis that the down-regulation of CD1d molecule leads to the decrease of NKT cell activation and the increase of blood pressure.
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DOI:10.1161/jaha.122.029179
发表时间:2023-07-04
期刊:JOURNAL OF THE AMERICAN HEART ASSOCIATION
影响因子:5.4
作者:Xiao, Xue;Hou, Cui-Liu;Zhang, Yun-Long;Yang, Hui;Wang, Xiao-Xiao;Wang, Hong-Xia
通讯作者:Wang, Hong-Xia
DOI:--
发表时间:2020
期刊:中国病理生理杂志
影响因子:--
作者:肖雪;侯翠柳;王筱筱;陈立瑞;杨慧;田翠;王红霞
通讯作者:王红霞
免疫蛋白酶体亚基β5i促进心肌重构的分子机制
- 批准号:81570207
- 项目类别:面上项目
- 资助金额:57.0万元
- 批准年份:2015
- 负责人:王红霞
- 依托单位:
urotensin II引起骨骼肌胰岛素抵抗的机制研究
- 批准号:81000343
- 项目类别:青年科学基金项目
- 资助金额:20.0万元
- 批准年份:2010
- 负责人:王红霞
- 依托单位:
国内基金
海外基金
