Downregulation of p53 by Insufficient CTCF in CD4+ T Cells Is an Important Factor Inducing Acute Graft-Versus-Host Disease.
Front Immunol
; 11: 568637, 2020.
Article
em En
| MEDLINE
| ID: mdl-33133081
ABSTRACT
Recent evidence indicates that p53 plays a protective role against various systemic autoimmune diseases by suppressing pro-inflammatory cytokine production and reducing the number of pathogenic T cells. However, whether abnormal p53 expression participates in the development of acute graft-versus-host disease (aGVHD) remains unclear. In this study, we demonstrated that p53 was downregulated in CD4+ T cells from patients with aGVHD compared with the non-aGVHD group. Furthermore, we confirmed that low expression of CCCTC-binding factor (CTCF) in CD4+ T cells from aGVHD cases is an important factor affecting histone H3K9/K14 hypoacetylation in the p53 promoter and p53 downregulation. Restoring CTCF expression in CD4+ T cells from aGVHD patients increased p53 amounts and corrected the imbalance of Th17 cells/Tregs. Taken together, these results provide novel insights into p53 downregulation in CD4+ T cells from aGVHD patients.
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Base de dados:
MEDLINE
Assunto principal:
Linfócitos T CD4-Positivos
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Proteína Supressora de Tumor p53
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Fator de Ligação a CCCTC
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Doença Enxerto-Hospedeiro
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article