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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.)

Current valid treatments for acute myeloid leukemia (AML) include chemotherapy and hematopoietic stem cell transplantation, which are defective and limited respectively. The insulin-like growth factor 1 receptor (IGF-1R) is up-regulated in many solid tumors; therefore, it may be a target for tumor therapy. Interestingly, IGF-1R is modified by SUMOylation, a type of reversible post-translational modification. In this study, we found that IGF-1R was increased in both cell lines and clinical samples of AML and was modified by SUMO-1. Furthermore, IGF-1, ligand of IGF-1R, induced the up-regulation of IGF-1R and increased the proliferation of leukemia cell line. After mutation of Lys 1025 and Lys 1100 in IGF-1R, the evolutionarily conserved lysine residues were identified as the SUMOylation sites of IGF-1R, because the SUMOylation of IGF-1R in these mutants was significantly inhibited. Furthermore, the cell proliferation mediated by IGF-1 was also reduced. After inhibition of UBC9, the activating enzyme of SUMOylation, co-expression of IGF-1R and SUMO-1 was down-regulated, and cell proliferation was also inhibited. However, cell apoptosis was not significantly affected. These results suggest that IGF-1R and its SUMOylation may be a new therapeutic target for strategy of AML. [ABSTRACT FROM AUTHOR]