AUTHOR=Hua Juan , Chen Yan , Fu Bin , Chen Xu , Xu Xue-jun , Yang Shuang-Hui , Chen Cong , Xu Ya-jing 

TITLE=Downregulation of p53 by Insufficient CTCF in CD4+ T Cells Is an Important Factor Inducing Acute Graft-Versus-Host Disease

JOURNAL=Frontiers in Immunology

VOLUME=11

YEAR=2020

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2020.568637

DOI=10.3389/fimmu.2020.568637

ISSN=1664-3224

ABSTRACT=<p>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<sup>+</sup> 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<sup>+</sup> T cells from aGVHD cases is an important factor affecting histone H3K9/K14 hypoacetylation in the <italic>p53</italic> promoter and p53 downregulation. Restoring CTCF expression in CD4<sup>+</sup> 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<sup>+</sup> T cells from aGVHD patients.</p>