Role of HMGB1 in regulation of STAT3 expression in CD4(+) T cells from patients with aGVHD after allogeneic hematopoietic stem cell transplantation.
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.
Department of Hematology, Xiangya Hospital, Central South University, Changsha, Hunan, China.
Ya-Jing
YJ
Xu
Department of Hematology, Xiangya Hospital, Central South University, Changsha, Hunan, China.
Lin
L
Li
Department of Hematology, Xiangya Hospital, Central South University, Changsha, Hunan, China.
Yan
Y
Chen
Department of Hematology, Xiangya Hospital, Central South University, Changsha, Hunan, China.
Bin
B
Fu
Department of Hematology, Xiangya Hospital, Central South University, Changsha, Hunan, China.
Deng-Shu
DS
Wu
Department of Hematology, Xiangya Hospital, Central South University, Changsha, Hunan, China.
Xiao-Lin
XL
Li
Department of Hematology, Xiangya Hospital, Central South University, Changsha, Hunan, China.
Xie-Lan
XL
Zhao
Department of Hematology, Xiangya Hospital, Central South University, Changsha, Hunan, China. Electronic address: xychenfp@qq.com.
Fang-Ping
FP
Chen
D000328:Adult; D015153:Blotting, Western; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002478:Cells, Cultured; D019175:DNA Methylation; D005260:Female; D005786:Gene Expression Regulation / Q000276:immunology*; D006086:Graft vs Host Disease / Q000209:etiology / Q000235:genetics / Q000276:immunology*; D024243:HMGB1 Protein / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods*; D006801:Humans; D008297:Male; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism; D058504:Th17 Cells / Q000276:immunology / Q000378:metabolism; D014184:Transplantation, Homologous
D024243:HMGB1 Protein; C585491:HMGB1 protein, human; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human
DNA methylation; HMGB1; STAT3; Th17; Treg; aGVHD