Humanized mouse model reveals T cell ANXA2 as a potential therapeutic target in ischemic stroke
Year: 2025
Type: article
Abstract: Stroke T cell studies in rodents have not been translated to human studies. The mechanism of cellular and molecular T cells changes after stroke remains incompletely understood. Thus, this study established a humanized mouse model after middle cerebral artery occlusion (MCAO) and identifies potential therapeutic targets of humanized T cell populations. Similar to patients with stroke, a proportion of T cells was decreased in peripheral blood of humanized T cell stroke mice. Using single-cell RNA sequencing (scRNA-seq), we identified Annexin A2 (ANXA2) as biomarker of humanized T cell subsets in MCAO, which was validated using human ischemic brain and peripheral blood. With small-molecule inhibitors Leu-Cys-Lys-Leu-Ser-Leu (LCKLSL), ANXA2 inhibition altered T CM and T EM subset in humanized mice. Furthermore, LCKLSL exhibited a neuroprotective role against ischemic damage, mitigating neuroinflammation, inhibiting T cell infiltration, and decreasing pro-inflammatory factors. Hence, this humanized T cell ischemic stroke model is more representative of the human disease than previous models; furthermore, ANXA2 is a meaningful therapeutic target.
Source: iScience
Authors: Tianyuan Zhang, Xiaojuan Zheng, Aijun Lu, Shuyuan Li, Keshen Li, Xiaoxiong Huang, Yanfang Liu, Wei Chen, Shengming Huang, Niu He, Chi Kwan Tsang, Hongcheng Mai, Anding Xu, Dan Lu
Language: English
Subfield: Neurology
Field: Neuroscience
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,240
Funders: National Natural Science Foundation of China, Sun Yat-sen University, Natural Science Foundation of Guangdong Province, Jiangsu Association for Science and Technology, Guangzhou Science and Technology Program key projects, Fundamental Research Funds for the Central Universities, Basic and Applied Basic Research Foundation of Guangdong Province
OpenAlex ID: W4409112152