CD4c-MetItgα4 T 细胞亚群促进小鼠神经炎症。
CD4c-MetItgα4 T cell subset promotes murine neuroinflammation.
机构信息
Department of Pathology and Immunology, Faculty of Medicine, University of Geneva, Geneva, Switzerland.
Department of Neurosciences, Division of Neurology, University Hospital of Geneva, Geneva, Switzerland.
出版信息
J Neuroinflammation. 2022 Apr 29;19(1):103. doi: 10.1186/s12974-022-02461-7.
OBJECTIVE
c-Met, a tyrosine kinase receptor, is the unique receptor for hepatocyte growth factor (HGF). The HGF/c-Met axis is reported to modulate cell migration, maturation, cytokine production, and antigen presentation. Here, we report that CD4c-Met T cells are detected at increased levels in experimental autoimmune encephalomyelitis (EAE), a mouse model of multiple sclerosis (MS).
METHODS
c-Met expression by CD4 T cells was analyzed mostly by flow cytometry and by immunohistochemistry from mice and human PBMCs. The in vivo role of CD4c-Met T cells was assessed in EAE.
RESULTS
CD4c-Met T cells found in the CNS during EAE peak disease are characterized by a pro-inflammatory phenotype skewed towards a Th1 and Th17 polarization, with enhanced adhesion and transmigration capacities correlating with increased expression of integrin α4 (Itgα4). The adoptive transfer of Itgα4-expressing CD4Vα3.2c-Met T cells induces increased disease severity compared to CD4Vα3.2c-Met T cells. Finally, CD4c-Met T cells are detected in the brain of MS patients, as well as in the blood with a higher level of Itgα4. These results highlight c-Met as an immune marker of highly pathogenic pro-inflammatory and pro-migratory CD4 T lymphocytes associated with neuroinflammation.
目的
c-Met 是一种酪氨酸激酶受体，是肝细胞生长因子 (HGF) 的唯一受体。据报道，HGF/c-Met 轴可调节细胞迁移、成熟、细胞因子产生和抗原呈递。在这里，我们报告在实验性自身免疫性脑脊髓炎 (EAE)，即多发性硬化症 (MS) 的小鼠模型中，CD4c-Met T 细胞的水平升高。
方法
通过流式细胞术和免疫组织化学从小鼠和人 PBMC 分析 CD4 T 细胞的 c-Met 表达。通过 EAE 评估 CD4c-Met T 细胞在体内的作用。
结果
在 EAE 疾病高峰期在中枢神经系统中发现的 CD4c-Met T 细胞具有促炎表型，偏向 Th1 和 Th17 极化，黏附和迁移能力增强，与整合素α4 (Itgα4) 的表达增加相关。与 CD4Vα3.2c-Met T 细胞相比，表达 Itgα4 的 CD4Vα3.2c-Met T 细胞的过继转移可诱导疾病严重程度增加。最后，在 MS 患者的大脑中以及血液中检测到 CD4c-Met T 细胞，其 Itgα4 水平更高。这些结果强调了 c-Met 作为与神经炎症相关的高致病性促炎和促迁移 CD4 T 淋巴细胞的免疫标志物。
Zotero 插件