实验性自身免疫性脑脊髓炎
整合素
自身免疫
免疫学
神经炎症
生物
白细胞介素17
自身免疫性疾病
白细胞外渗
细胞生物学
T细胞
整合素αM
癌症研究
多发性硬化
细胞粘附分子
细胞
炎症
免疫系统
抗体
遗传学
作者
Eunchong Park,William E. Barclay,Alejandro Barrera,Tzu-Chieh Liao,Harmony R. Salzler,Timothy E. Reddy,Mari L. Shinohara,Maria Ciofani
出处
期刊:Science immunology
[American Association for the Advancement of Science (AAAS)]
日期:2023-10-27
卷期号:8 (88)
被引量:2
标识
DOI:10.1126/sciimmunol.adg7597
摘要
Multiple sclerosis (MS) is an autoimmune disease of the central nervous system (CNS) caused by CNS-infiltrating leukocytes, including TH17 cells that are critical mediators of disease pathogenesis. Although targeting leukocyte trafficking is effective in treating autoimmunity, there are currently no therapeutic interventions that specifically block encephalitogenic TH17 cell migration. Here, we report integrin α3 as a TH17 cell-selective determinant of pathogenicity in experimental autoimmune encephalomyelitis. CNS-infiltrating TH17 cells express high integrin α3, and its deletion in CD4+ T cells or Il17a fate-mapped cells attenuated disease severity. Mechanistically, integrin α3 enhanced the immunological synapse formation to promote the polarization and proliferation of TH17 cells. Moreover, the transmigration of TH17 cells into the CNS was dependent on integrin α3, and integrin α3 deficiency enhanced the retention of CD4+ T cells in the perivascular space of the blood-brain barrier. Integrin α3-dependent interactions continuously maintain TH17 cell identity and effector function. The requirement of integrin α3 in TH17 cell pathogenicity suggests integrin α3 as a therapeutic target for MS treatment.
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