SCI文章
优秀科研成果展示(一)
题目:浆细胞样树突状细胞通过调节性T细胞发挥对缺血性脑卒中的保护作用
摘要:调节性T细胞(Regulatory T cells, Tregs)是缺血性脑卒中后炎症性脑损伤的重要保护调节器,浆细胞样树突状细胞(Plasmacytoid dendritic cells, pDCs)具有激活Tregs的功能。但有关pDCs激活Tregs在缺血性脑卒中中的作用和机制尚不清楚。在本研究中,我们发现在大脑中动脉阻塞模型(Middle cerebral artery occlusion, MCAO)小鼠脑内出现pDCs的升高;采用pDCs特异性抗体120G8删除pDCs后会加剧MCAO小鼠脑损伤、外周促炎反应并降低小鼠体内Tregs的数目。此外,体外混合淋巴细胞反应实验结果表明模型小鼠脾脏来源的pDCs能显著刺激Tregs的增殖分化,同时伴随着pDCs表面IDO1分子表达升高。结论:在中风病理条件下,pDCs可通过启动Tregs发挥对脑缺血再灌注损伤的保护作用。本研究从能特异性激活Treg的pDCs角度出发,为防治缺血性脑损伤提供了新的治疗靶点和理论指导。
Title: Plasmacytoid Dendritic Cells Protect Against Middle Cerebral Artery Occlusion Induced Brain Injury by Priming Regulatory T Cells
Abstract: Regulatory T cells (Tregs) play an anti-inflammatory effect to protect against ischemic stroke. Plasmacytoid dendritic cells (pDCs) can induce regulatory T cells tolerance in sterile-inflammation conditions. However, whether and how pDCs-mediated Tregs response play a part in the pathology of ischemic stroke remains unclear. In this study, we showed that pDCs were increased in the brain of middle cerebral artery occlusion (MCAO) mice. Depletion of pDCs with 120G8 exacerbated MCAO-induced brain injury, peripheral pro-inflammation response and decreased the systemic Tregs in mice. Furthermore, the data of mixed lymphocyte reaction (MLR) in vitro demonstrate that splenic pDCs from MCAO mice can significantly promote Tregs proliferation, accompanying with the increased expression of indoleamine 2,3-dioxygenase 1 (IDO1) on pDCs. Taken together, the findings here suggested that under the pathologic state of stroke, pDCs protect against MCAO-induced brain injury by priming Tregs, illustrating that pDCs represented as a therapeutic target for the prevention of ischemic brain injury.
第一作者:陈晨
首都医科大学细胞生物学博士研究生,现任首都医科大学附属北京潞河医院助理研究员。研究方向:缺血性脑血管病的免疫机制探讨。曾获得北京市自然科学基金、首都医科大学科研培育基金、通州区科委及潞河医院科研基金多项资助。累计发表SCI论文8篇,中文核心3篇。
通讯作者:耿晓坤,
耿晓坤,首都医科大学附属北京潞河医院神经内科主任、主任医师、副教授、硕士生导师。国家自然科学基金评审专家;美国韦恩州立大学客座教授;北京神经内科学会青委会主任委员、北京神经内科学会介入分会副主任委员、北京医师学会神经介入分会青委常委、任《Neurological Research》、《中国卒中杂志》特邀主编,以及《Environmental Disease》、《Brain Circulation》等多个国际杂志编委。长期从事神经介入工作和脑卒中神经保护研究,完成各类神经介入手术3000余例。入选北京市“科技新星”及“北京市优秀人才”,主持:国家自然科学基金面上项目、国家自然科学基金青年项目、北京市“科技新星”计划、北京市教委科技计划项目及北京市优秀人才等多项国家级、省部级科研项目,参与科技部国家重点研发计划。近5年发表SCI论文80余篇,累计影响因子大于180。其中单篇最高影响因子13.6,执笔《中国缺血性脑卒中血管内治疗指导规范》临床指南