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Double-negative T cells remarkably promote neuroinflammation after ischemic stroke.


ABSTRACT: 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-? 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.

SUBMITTER: Meng H 

PROVIDER: S-EPMC6431175 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

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Double-negative T cells remarkably promote neuroinflammation after ischemic stroke.

Meng Hailan H   Zhao Haoran H   Cao Xiang X   Hao Junwei J   Zhang He H   Liu Yi Y   Zhu Min-Sheng MS   Fan Lizhen L   Weng Leihua L   Qian Lai L   Wang Xiaoying X   Xu Yun Y  

Proceedings of the National Academy of Sciences of the United States of America 20190228 12


CD3<sup>+</sup>CD4<sup>-</sup>CD8<sup>-</sup> 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 immu  ...[more]

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