当前位置:科学网首页 > 小柯机器人 >详情
Treg细胞来源骨桥蛋白促进白质修复机制
作者:小柯机器人 发布时间:2021/5/21 20:09:31

美国匹兹堡大学Xiaoming Hu团队取得一项新成果。他们发现调节性T(Treg)细胞来源的骨桥蛋白促进缺血性中风后小胶质细胞介导的白质修复。相关论文于2021年5月19日发表于国际顶尖学术期刊《免疫》杂志上。

使用单细胞RNA测序和流式细胞仪,他们发现Treg细胞在小鼠实验性中风后1至5周渗入大脑。Treg细胞的选择性消耗减少了少突胶质生成、白质修复和中风后的功能恢复。转录组学分析揭示了脑浸润Treg细胞对其他免疫细胞(包括单核细胞系细胞)的有效免疫调节作用。小胶质细胞的消耗,但不是T细胞淋巴细胞减少,减轻了转移Treg细胞对白质再生的有益作用。

从机制上讲,源自Treg细胞的骨桥蛋白通过小胶质细胞上的整联蛋白受体起作用,以增强小胶质细胞的修复活性,从而促进少突胶质生成和白质修复。通过中风后递送IL-2:IL-2抗体复合物来增加Treg细胞数量,可长期改善白质完整性并挽救神经功能。这些发现揭示了Treg细胞是中风恢复的神经修复靶标。

研究人员表示,Treg细胞对长期组织修复产生有益作用的确切机制仍然未知。

附:英文原文

Title: Treg cell-derived osteopontin promotes microglia-mediated white matter repair after ischemic stroke

Author: Ligen Shi, Zeyu Sun, Wei Su, Fei Xu, Di Xie, Qingxiu Zhang, Xuejiao Dai, Kartik Iyer, T. Kevin Hitchens, Lesley M. Foley, Sicheng Li, Donna B. Stolz, Kong Chen, Ying Ding, Angus W. Thomson, Rehana K. Leak, Jun Chen, Xiaoming Hu

Issue&Volume: 2021-05-19

Abstract: The precise mechanisms underlying the beneficial effects of regulatory T (Treg) cellson long-term tissue repair remain elusive. Here, using single-cell RNA sequencingand flow cytometry, we found that Treg cells infiltrated the brain 1 to 5 weeks afterexperimental stroke in mice. Selective depletion of Treg cells diminished oligodendrogenesis,white matter repair, and functional recovery after stroke. Transcriptomic analysesrevealed potent immunomodulatory effects of brain-infiltrating Treg cells on otherimmune cells, including monocyte-lineage cells. Microglia depletion, but not T celllymphopenia, mitigated the beneficial effects of transferred Treg cells on white matterregeneration. Mechanistically, Treg cell-derived osteopontin acted through integrinreceptors on microglia to enhance microglial reparative activity, consequently promotingoligodendrogenesis and white matter repair. Increasing Treg cell numbers by deliveringIL-2:IL-2 antibody complexes after stroke improved white matter integrity and rescuedneurological functions over the long term. These findings reveal Treg cells as a neurorestorativetarget for stroke recovery.

DOI: 10.1016/j.immuni.2021.04.022

Source: https://www.cell.com/immunity/fulltext/S1074-7613(21)00184-9

期刊信息

Immunity:《免疫》,创刊于1994年。隶属于细胞出版社,最新IF:21.522
官方网址:https://www.cell.com/immunity/home
投稿链接:https://www.editorialmanager.com/immunity/default.aspx