Chen Chen, Chencheng Zhang, Cuiying Liu, Xiaokun Geng
China-America Institute of Neuroscience, Beijing Luhe Hospital, Capital Medical University, Beijing, China.
Front Cell Neurosci. 2020 Jan 31;14:8. doi: 10.3389/fncel.2020.00008. eCollection 2020.
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) 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.
调节性T细胞(Tregs)发挥抗炎作用以预防缺血性中风。浆细胞样树突状细胞(pDCs)可在无菌炎症条件下诱导调节性T细胞耐受。然而,pDCs介导的Tregs反应是否以及如何在缺血性中风的病理过程中发挥作用仍不清楚。在本研究中,我们发现大脑中动脉闭塞(MCAO)小鼠脑内的pDCs数量增加。用120G8清除pDCs会加重MCAO诱导的脑损伤、外周促炎反应,并降低小鼠体内的全身Tregs水平。此外,混合淋巴细胞反应(MLR)数据表明,MCAO小鼠的脾脏pDCs可显著促进Tregs增殖,同时pDCs上吲哚胺2,3-双加氧酶1(IDO1)的表达增加。综上所述,此处的研究结果表明,在中风的病理状态下,pDCs通过启动Tregs来保护小鼠免受MCAO诱导的脑损伤,这说明pDCs可作为预防缺血性脑损伤的治疗靶点。