期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 116, 期 12, 页码 5558-5563出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1814394116
关键词
ischemic stroke; neuroinflammation; DNTs; FasL; T cell-mediated immunity
资金
- National Natural Science Foundation of China [81630028, 81230026, 81701168, 81701170]
- Science and Technology Department of Jiangsu Province [BE2016610]
- Jiangsu Province Key Medical Discipline [ZDXKA2016020]
CD3(+)CD4(-)CD8(-) T cells (double-negative T cells; DNTs) have diverse functions in peripheral immune-related diseases by regulating immunological and inflammatory homeostasis. However, the functions of DNTs in the central nervous system remain unknown. Here, we found that the levels of DNTs were dramatically increased in both the brain and peripheral blood of stroke patients and in a mouse model in a time-dependent manner. The infiltrating DNTs enhanced cerebral immune and inflammatory responses and exacerbated ischemic brain injury by modulating the FasL/PTPN2/TNF-alpha signaling pathway. Blockade of this pathway limited DNT-mediated neuroinflammation and improved the outcomes of stroke. Our results identified a critical function of DNTs in the ischemic brain, suggesting that this unique population serves as an attractive target for the treatment of ischemic stroke.
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