Insufficient phosphorylation of STAT5 in Tregs inhibits the expression of BLIMP-1 but not IRF4, reduction the proportion of Tregs in pediatric aplastic anemia
Lifen Huang,
Junbin Huang,
Nannan Tang,
Hongman Xue,
Shaofen Lin,
Su Liu,
Qihui Chen,
Yinsi Lu,
Qian Liang,
Yun Wang,
Qingqing Zhu,
Guoxing Zheng,
Yun Chen,
Chengming Zhu,
Chun Chen
Affiliations
Lifen Huang
Pediattic Hematology Laboratory, Division of Hematology/Oncology, Department of Pediatrics, The Seventh Affifiliated Hospital, Sun Yat-sen University, 518107, Shenzhen, Guangdong, China
Junbin Huang
Pediattic Hematology Laboratory, Division of Hematology/Oncology, Department of Pediatrics, The Seventh Affifiliated Hospital, Sun Yat-sen University, 518107, Shenzhen, Guangdong, China
Nannan Tang
Pediattic Hematology Laboratory, Division of Hematology/Oncology, Department of Pediatrics, The Seventh Affifiliated Hospital, Sun Yat-sen University, 518107, Shenzhen, Guangdong, China
Hongman Xue
Pediattic Hematology Laboratory, Division of Hematology/Oncology, Department of Pediatrics, The Seventh Affifiliated Hospital, Sun Yat-sen University, 518107, Shenzhen, Guangdong, China
Shaofen Lin
Department of Pediatric Hematopathy, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, 510000, Guangzhou, Guangdong, China
Su Liu
Pediattic Hematology Laboratory, Division of Hematology/Oncology, Department of Pediatrics, The Seventh Affifiliated Hospital, Sun Yat-sen University, 518107, Shenzhen, Guangdong, China
Qihui Chen
Department of Pediatric Hematopathy, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, 510000, Guangzhou, Guangdong, China
Yinsi Lu
Department of Pathology, The Seventh Affifiliated Hospital, Sun Yat-sen University, 518107, Shenzhen, Guangdong, China
Qian Liang
Department of Pathology, The Seventh Affifiliated Hospital, Sun Yat-sen University, 518107, Shenzhen, Guangdong, China
Yun Wang
Department of Pathology, The Seventh Affifiliated Hospital, Sun Yat-sen University, 518107, Shenzhen, Guangdong, China
Qingqing Zhu
Department of Pathology, The Seventh Affifiliated Hospital, Sun Yat-sen University, 518107, Shenzhen, Guangdong, China
Guoxing Zheng
Department of Pathology, The Seventh Affifiliated Hospital, Sun Yat-sen University, 518107, Shenzhen, Guangdong, China
Yun Chen
Department of Pathology, The Seventh Affifiliated Hospital, Sun Yat-sen University, 518107, Shenzhen, Guangdong, China; Corresponding author.
Chengming Zhu
Department of Pathology, The Seventh Affifiliated Hospital, Sun Yat-sen University, 518107, Shenzhen, Guangdong, China; Corresponding author.
Chun Chen
Pediattic Hematology Laboratory, Division of Hematology/Oncology, Department of Pediatrics, The Seventh Affifiliated Hospital, Sun Yat-sen University, 518107, Shenzhen, Guangdong, China; Corresponding author.
Deficiency in regulatory T cells (Tregs) is an important mechanism underlying the pathogenesis of pediatric aplastic anemia, but its specific mechanism is unclear. In our study, we aimed to investigate whether IL-2/STAT5 can regulate the proliferation of Tregs in aplastic anemia (AA) by regulating their expression of B lymphocyte-induced mature protein-1 (BLIMP-1) or interferon regulatory factor 4 (IRF4). Through clinical research and animal experiments, we found that poor activation of the IL-2/STAT5 signaling pathway may leads to low expression of BLIMP-1 in Tregs of children with AA, which leads to defects in the differentiation and proliferation of Tregs in AA. In AA model mice, treatment with IL-2c reversed the decrease in Treg proportions and reduction in Blimp-1 expression in Tregs by increasing the phosphorylation of Stat5 in Tregs. In AA, deficiency of IRF4 expression in Tregs is closely related to the deficiency of Tregs, but is not regulated by the IL-2/STAT5 pathway.