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https://doi.org/10.1161/str.51.suppl_1.wmp76
Copy DOIJournal: Stroke | Publication Date: Feb 1, 2020 |
Background: The interleukin (IL)-33 could promote proliferation of regulatory T lymphocytes (Tregs) which are negatively related with brain damage after ischemic stroke. How IL-33 works on Tregs after stroke is unclear. The purpose of this study was to investigate the role of IL-33 for Tregs-mediated neuroprotection and further expounded the mechanisms of protection in mice. Methods: In vitro study, primary mice neuronal cells were subjected to 3h oxygen-glucose deprivation (OGD). The vehicle or drug conditioned Tregs were applied to neurons at the time of induction of hypoxia respectively. Neuronal apoptosis, Tregs related cytokines were measured by MTT assay, Western blotting and enzyme-linked immune-sorbent assay (ELISA). In vivo study, Tregs were depleted by intraperitoneal administration of anti-CD25Ab. Intraperitoneal injection of IL-33 immediately post 60 min transient middle cerebral artery occlusion (tMCAO) modeling. The neurological function test at days 1, 3, 5, 7 and 14 after tMCAO. Infarct volume, Brain edema, cell death, percentage of Tregs and related cytokines were respectively measured by 2,3,5-triphenyltetrazolium chloride or MAP2 staining, dry-wet method, TUNEL staining, flow cytometry and immunofluorescence, Western blotting and ELISA. Results: The supernatant of IL-33-treated Tregs reduced neuronal apoptosis in the OGD model meanwhile elevated the production of Tregs related cytokines IL-10, IL-35 and TGF- β in vitro. Intraperitoneal administration of IL-33 significantly reduced infarct volume and stroke-induced cell death and improved sensorimotor functions. Notably, the protective effect of IL-33 was abolished in mice depleted of Tregs. IL-33 increased CD4+CD25+Foxp3+ Tregs in spleens, blood, and brain in vivo. Yet, ST2 blocking muted these IL-33 activities. Mechanistically, the protection of IL-33 was associated with reduced apoptosis protein and production of Tregs related cytokine. Conclusions: This study elucidated that IL-33 afforded neuroprotection against ischemic brain injury by enhancing ST2-dependent regulatory T-cell expansion and activation, which suggested a promising immune modulatory target for the treatment of stroke.
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