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Role of cellular prion protein in splenic CD4(+) T cell differentiation in cerebral ischaemic/reperfusion
OBJECTIVE: Cellular prion protein (PrP(C)), 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 i...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8528449/ https://www.ncbi.nlm.nih.gov/pubmed/34524735 http://dx.doi.org/10.1002/acn3.51453 |
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author | Zhang, Baizhuo Yin, Xiang Lang, Yue Han, Xiaoou Shao, Jie Bai, Rongrong Cui, Li |
author_facet | Zhang, Baizhuo Yin, Xiang Lang, Yue Han, Xiaoou Shao, Jie Bai, Rongrong Cui, Li |
author_sort | Zhang, Baizhuo |
collection | PubMed |
description | OBJECTIVE: Cellular prion protein (PrP(C)), 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(+)PrP(C+) 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(+) PrP(C+) 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, PrP(C)‐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 PrP(C) deficiency enhanced apoptosis. INTERPRETATION: PrP(C) 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. |
format | Online Article Text |
id | pubmed-8528449 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-85284492021-10-27 Role of cellular prion protein in splenic CD4(+) T cell differentiation in cerebral ischaemic/reperfusion Zhang, Baizhuo Yin, Xiang Lang, Yue Han, Xiaoou Shao, Jie Bai, Rongrong Cui, Li Ann Clin Transl Neurol Research Article OBJECTIVE: Cellular prion protein (PrP(C)), 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(+)PrP(C+) 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(+) PrP(C+) 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, PrP(C)‐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 PrP(C) deficiency enhanced apoptosis. INTERPRETATION: PrP(C) 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. John Wiley and Sons Inc. 2021-09-15 /pmc/articles/PMC8528449/ /pubmed/34524735 http://dx.doi.org/10.1002/acn3.51453 Text en © 2021 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made. |
spellingShingle | Research Article Zhang, Baizhuo Yin, Xiang Lang, Yue Han, Xiaoou Shao, Jie Bai, Rongrong Cui, Li Role of cellular prion protein in splenic CD4(+) T cell differentiation in cerebral ischaemic/reperfusion |
title | Role of cellular prion protein in splenic CD4(+) T cell differentiation in cerebral ischaemic/reperfusion |
title_full | Role of cellular prion protein in splenic CD4(+) T cell differentiation in cerebral ischaemic/reperfusion |
title_fullStr | Role of cellular prion protein in splenic CD4(+) T cell differentiation in cerebral ischaemic/reperfusion |
title_full_unstemmed | Role of cellular prion protein in splenic CD4(+) T cell differentiation in cerebral ischaemic/reperfusion |
title_short | Role of cellular prion protein in splenic CD4(+) T cell differentiation in cerebral ischaemic/reperfusion |
title_sort | role of cellular prion protein in splenic cd4(+) t cell differentiation in cerebral ischaemic/reperfusion |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8528449/ https://www.ncbi.nlm.nih.gov/pubmed/34524735 http://dx.doi.org/10.1002/acn3.51453 |
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