Objective: Cellular prion protein (PrPC), the primary form of prion diseases pathogen, has received increasing attention for its protective effect against ischaemic stroke. Little is known about its role in peripheral immune responses after cerebral ischaemia/reperfusion (I/R) injury. This study is to detect the variation of splenic CD4+ T lymphocytes differentiation and the concentration of inflammatory cytokines after murine cerebral I/R injury in the context of PRNP expression as well as its influence on the ischaemic neuronal apoptosis. Methods: We established the cerebral ischaemic murine model of different PRNP genotypes. We detected the percentage of splenic CD4+PrPC+ T cells of PRNP wild-type mice and the ratio of splenic Th1/2/17 lymphocytes of mice of different PRNP expression. The relevant inflammatory cytokines were then measured. Oxygen glucose deprivation/reperfusion (OGD/R) HT22 mouse hippocampal neurons were co-cultured with the T-cell-conditioned medium harvested from the spleen of modelled mice and then the neuronal apoptosis was detected. Results: CD4+ PrPC+ T lymphocytes in wild-type mice elevated after MCAO/R. PRNP expression deficiency led to an elevation of Th1/17 phenotypes and the promotion of pro-inflammatory cytokines, while PRNP overexpression led to the elevation of Th2 phenotype and upregulation of anti-inflammatory cytokines. In addition, PrPC-overexpressed CD4+T cells weakened the apoptosis of OGD/R HT-22 murine hippocampal neurons caused by MCAO/R CD4+ T-cell-conditioned medium, while PrPC deficiency enhanced apoptosis. Interpretation: PrPC works as a neuron protector in the CNS when I/R injury occurs and affects the peripheral immune responses and defends against stroke-induced neuronal apoptosis.
CITATION STYLE
Zhang, B., Yin, X., Lang, Y., Han, X., Shao, J., Bai, R., & Cui, L. (2021). Role of cellular prion protein in splenic CD4+ T cell differentiation in cerebral ischaemic/reperfusion. Annals of Clinical and Translational Neurology, 8(10), 2040–2051. https://doi.org/10.1002/acn3.51453
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