2. Academic Validation
  3. Rapamycin ameliorates immune-mediated aplastic anemia by inhibiting the proliferation and metabolism of T cells

Rapamycin ameliorates immune-mediated aplastic anemia by inhibiting the proliferation and metabolism of T cells

  • Biochem Biophys Res Commun. 2019 Oct 15;518(2):212-218. doi: 10.1016/j.bbrc.2019.08.034.
Sheng-Li Liu 1,  Yan-Man Zhou 2,  Da-Bin Tang 1,  Neng Zhou 1,  Wei-Wei Zheng 1,  Zhong-Hua Tang 1,  Cai-Wen Duan 3,  Jing Chen 4
Affiliations

Affiliations

  • 1 Key Laboratory of Pediatric Hematology and Oncology Ministry of Health and Pediatric Translational Medicine Institute, Shanghai, 200025, China; Department of Hematology and Oncology, Shanghai Children's Medical Center, Shanghai Collaborative Innovation Center for Translational Medicine, Shanghai, 200025, China; Department of Pharmacology and Chemical Biology, Shanghai Jiao Tong University School of Medicine (SJTU-SM), Shanghai, 200025, China.
  • 2 Department of Endocrinology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine (SJTU-SM), Shanghai, 200025, China.
  • 3 Key Laboratory of Pediatric Hematology and Oncology Ministry of Health and Pediatric Translational Medicine Institute, Shanghai, 200025, China; Department of Hematology and Oncology, Shanghai Children's Medical Center, Shanghai Collaborative Innovation Center for Translational Medicine, Shanghai, 200025, China; Department of Pharmacology and Chemical Biology, Shanghai Jiao Tong University School of Medicine (SJTU-SM), Shanghai, 200025, China. Electronic address: duancaiwen@163.com.
  • 4 Key Laboratory of Pediatric Hematology and Oncology Ministry of Health and Pediatric Translational Medicine Institute, Shanghai, 200025, China; Department of Hematology and Oncology, Shanghai Children's Medical Center, Shanghai Collaborative Innovation Center for Translational Medicine, Shanghai, 200025, China; Department of Pharmacology and Chemical Biology, Shanghai Jiao Tong University School of Medicine (SJTU-SM), Shanghai, 200025, China. Electronic address: chenjingscmc@hotmail.com.
PMID: 31434610 DOI: 10.1016/j.bbrc.2019.08.034
Abstract

Aplastic anemia (AA) is a serious blood system disease that threatens human health. At present, the main cause of this disease is believed to be immune hyperfunction. However, the specific metabolic mode involved in the occurrence of lymphocytes in AA is still unknown. In addition, whether rapamycin, a specific blocker of the mTOR signaling pathway, plays a therapeutic role by inhibiting lymphocyte metabolism remains unclear. We induced an AA mouse model through the classical immune-mediated pathway and simultaneously administered rapamycin intervention therapy. First, the AA-associated phenotypic changes and the efficacy of rapamycin in the treatment of AA were discussed. Second, the proliferation and metabolic pathway of bone marrow (BM) lymphocytes in AA and the effect of rapamycin on this process were determined. Finally, the expression levels of mTOR pathway-related proteins were analyzed. By inhibiting the mTOR signaling pathway, rapamycin could ameliorate the phenotype of the immune-mediated AA model and inhibit the proliferation of T cells by preventing cell cycle transition from G0 to G1 phase. Moreover, we found that mitochondrial Oxidative Phosphorylation is involved in the metabolic reprogramming of T cells in AA and that rapamycin can inhibit this process. We confirmed that mitochondrial Oxidative Phosphorylation is involved in the metabolic reprogramming of T cells in AA and further extended the mechanism of rapamycin in treating AA by inhibiting the mTOR signaling pathway. This viewpoint may provide a new therapeutic idea for clinical applications.

Keywords

Aplastic anemia; Lymphocyte; Metabolic reprogramming; Rapamycin; mTOR signaling pathway.

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