1. Role of HMGB1 in regulation of STAT3 expression in CD4(+) T cells from patients with aGVHD after allogeneic hematopoietic stem cell transplantation.
- Author
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Xu YJ, Li L, Chen Y, Fu B, Wu DS, Li XL, Zhao XL, and Chen FP
- Subjects
- Adult, Blotting, Western, CD4-Positive T-Lymphocytes metabolism, Cells, Cultured, DNA Methylation, Female, Graft vs Host Disease etiology, Graft vs Host Disease genetics, HMGB1 Protein genetics, HMGB1 Protein metabolism, Hematopoietic Stem Cell Transplantation adverse effects, Humans, Male, RNA Interference, Reverse Transcriptase Polymerase Chain Reaction, STAT3 Transcription Factor genetics, STAT3 Transcription Factor metabolism, T-Lymphocytes, Regulatory immunology, T-Lymphocytes, Regulatory metabolism, Th17 Cells immunology, Th17 Cells metabolism, Transplantation, Homologous, CD4-Positive T-Lymphocytes immunology, Gene Expression Regulation immunology, Graft vs Host Disease immunology, HMGB1 Protein immunology, Hematopoietic Stem Cell Transplantation methods, STAT3 Transcription Factor immunology
- Abstract
Treg/Th17 balance plays a critical role in maintaining immune homeostasis of acute graft-versus-host disease (aGVHD) patients. STAT3 is an important factor involved in the instability of Treg and the promotion of Th17. HMGB1 is a cytokine mediator of inflammation and an important chromatin protein regulating gene transcription. In this study, we found that the expressions of HMGB1 and STAT3 were higher in CD4(+) T cells of patients with aGVHD compared with those without aGVHD, and the HMGB1 expression was positively correlated with the STAT3 expression. Simultaneously, their expressions were positively correlated with the severity of the aGVHD. We also demonstrated that HMGB1 could regulate the expression of STAT3 by modulation of its DNA methylation in CD4(+) T cells, moreover downregulated HMGB1 in aGVHD CD4(+) T cells could change the ratio of Treg/Th17. These data strongly suggest that HMGB1 plays a crucial role in the regulation of Treg/Th17 and progression of aGVHD., (Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.)
- Published
- 2015
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