Regulatory T cells and CD20<sup>+</sup>B cells in pediatric very severe aplastic anemia: possible clinical markers for evaluating the therapeutic efficacy and prognosis

Fang, Junyue; Lin, Li; Wang, Ying; Lin, Dijin; Liu, Chunyue; Sunlong, Qiaozi; Li, Xianghua

doi:10.1080/10245332.2018.1498566

Cited by 5 publications

(3 citation statements)

References 35 publications

(32 reference statements)

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“…In recent years, research on the roles of shikonin in human health has gradually deepened. Accumulating evidence suggests that shikonin can suppress tumor growth and overcome the resistance to chemotherapy drugs in tumor cells [10]. Tang et al [11] suggested that shikonin can significantly inhibit the proliferation of esophageal cancer cells by regulating the HIF1α/PKM2 signaling pathway.…”

Section: Mediators Of Inflammationmentioning

confidence: 99%

“…We speculate that the changes in CTL function were due to shikonin-mediated inhibition of PKM2 levels in mDCs, which in turn regulated the expression of mDC costimulatory molecules and inflammatory factors. Recently, the role of Treg cell population in SAA pathogenesis has attracted much research attention [10]. Tregs are believed to control the progression of autoimmunity in AA by suppressing overactive T cells and preventing the antigen presentation process of mDCs [23].…”

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confidence: 99%

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Effects of Shikonin on the Functions of Myeloid Dendritic Cells in a Mouse Model of Severe Aplastic Anemia

Zheng

Liu

Shao

et al. 2020

Mediators of Inflammation

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This study is aimed at investigating the effects of shikonin, a pyruvate kinase M2 (PKM2) inhibitor, on the functions of myeloid dendritic cells (mDCs) in a mouse model of severe aplastic anemia (AA) generated by total body irradiation and lymphocyte infusion. Flow cytometry and qPCR were used to determine the proportions of PKM2+ mDCs and other immune indicators in the AA mice. Glucose consumption level, pyruvate generation level, and ATP content were used to determine the level of glycolytic metabolism in the mDCs. The survival rates of AA mice were evaluated after the administration of shikonin or the immunosuppressive agent cyclosporin A. The AA mice displayed pancytopenia, decreased CD4+/CD8+ cell ratio, increased perforin and granzyme levels in CD8+ cells, increased costimulatory CD80 and CD86 expressions, and inadequate regulatory T cell number. In vivo animal experiments showed that the shikonin-mediated inhibition of the PKM2 expression in mice was associated with high survival rates. In addition, the administration of cyclosporin A or shikonin decreased the expression of cytotoxic molecules and costimulatory CD80 and CD86 on CD8+ cells. Taken together, the results of this study indicated that shikonin could inhibit the activation and proliferation of mDCs as well as the activation of downstream cytotoxic T cells by reducing the PKM2 level in mDCs.

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Section: Mediators Of Inflammationmentioning

confidence: 99%

mentioning

confidence: 99%

Effects of Shikonin on the Functions of Myeloid Dendritic Cells in a Mouse Model of Severe Aplastic Anemia

Zheng

Liu

Shao

et al. 2020

Mediators of Inflammation

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“…The most favored model is that of a dysregulated immune system leading to autoreactive T-cell destruction of hematopoietic stem and progenitor cells. This is well reflected in SAA patients with expanded CD8+ T-cells and increased TNFα and INFγ levels (17)(18)(19). However, the same immunological abnormality is rarely found in NSAA.…”

Section: Discussionmentioning

confidence: 92%

Cyclosporine Monotherapy in Pediatric Patients With Non-severe Aplastic Anemia: A Retrospective Analysis

Yang

et al. 2022

Front. Med.

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ObjectiveThe management of children with non-severe aplastic anemia (NSAA) is undefined and the efficacies and benefits of immunosuppressive therapy remain inconsistent. The study aimed to investigate the efficacy of Cyclosporine (CsA) monotherapy for pediatric NSAA.MethodsClinical data of children with NSAA who had been treated with CsA monotherapy at the outpatient department of Beijing Children's Hospital, Capital Medical University, National Children's Medical Center from January 2017 to March 2021 was collected retrospectively. Patients who had been treated <1 years until the end of follow-up were excluded. Transfusion-independent NSAA was further divided into moderate NSAA and mild NSAA according to the degree of cytopenia. Progression was defined as the development of transfusion-dependent AA or SAA and relapse was considered when treatment failed after initial response.ResultsA total of 95 pediatric patients with NSAA were enrolled in this study with 49 (51.6%) patients confirmed as mild NSAA, 38 (40%) as moderate NSAA and 8 (8.4%) as transfusion-dependent NSAA. The median treatment time of CsA was 22 (12–44) months. The overall response rate (ORR) was 57.9%, with 30.5% CR and 27.4% PR. Unexpectedly, patients with mild NSAA acquired lowest ORR (46.9%), then patients with moderate NSAA (63.2%), while 8 patients who were transfusion-dependent all had an active response to CsA. The granulocyte and megakaryocyte response was 46.9 and 55.8% respectively, while the erythrocyte response rate was as low as 22.5%. Univariate analyses revealed that patients with lower platelet count and higher interleukin 10 level predict an active response to CsA while higher level of fetal hemoglobin (HbF) tended to be a negative factor. Data of Treg cells before and after 1 year's treatment was available in a total number of 40 patients. Paired comparison found that the percentage of Treg cells in CD4+ T cells was decreased after 1 year's treatment of CsA (6.78 ± 2.72 vs. 5.23 ± 2.06, P = 0.001),both in responders and non-responders. The degree of decline in Treg cells between two distinctive response groups had no significant difference (P>0.05). With a median follow-up time of 22 months, 10.9% of responders relapsed and maintained NSAA while 27.5% of non-responders progressed to SAA or became transfusion-dependent. The overall progression rate was 11.6%.ConclusionCsA monotherapy had heterogeneous effects in the treatment of children NSAA Treatment approaches should be hierarchical and individual in clinical. Patients with lower platelet count and higher interleukin 10 level predicted an active response to CsA. While higher level of fetal hemoglobin (HbF) tended to be a negative factor. The percentage of Treg cells in CD4+ T cells was decreased broadly after treatment.

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Reduced regulatory effects of bone marrow-derived mesenchymal stem cells on activated T lymphocytes and Th1/Th2 cytokine secretion in children with aplastic anemia

Guo,

Weng,

Wang

et al. 2023

Clin Exp Med

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Regulatory T cells and CD20⁺B cells in pediatric very severe aplastic anemia: possible clinical markers for evaluating the therapeutic efficacy and prognosis

Cited by 5 publications

References 35 publications

Effects of Shikonin on the Functions of Myeloid Dendritic Cells in a Mouse Model of Severe Aplastic Anemia

Effects of Shikonin on the Functions of Myeloid Dendritic Cells in a Mouse Model of Severe Aplastic Anemia

Cyclosporine Monotherapy in Pediatric Patients With Non-severe Aplastic Anemia: A Retrospective Analysis

Reduced regulatory effects of bone marrow-derived mesenchymal stem cells on activated T lymphocytes and Th1/Th2 cytokine secretion in children with aplastic anemia

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Regulatory T cells and CD20+B cells in pediatric very severe aplastic anemia: possible clinical markers for evaluating the therapeutic efficacy and prognosis

Cited by 5 publications

References 35 publications

Effects of Shikonin on the Functions of Myeloid Dendritic Cells in a Mouse Model of Severe Aplastic Anemia

Effects of Shikonin on the Functions of Myeloid Dendritic Cells in a Mouse Model of Severe Aplastic Anemia

Cyclosporine Monotherapy in Pediatric Patients With Non-severe Aplastic Anemia: A Retrospective Analysis

Reduced regulatory effects of bone marrow-derived mesenchymal stem cells on activated T lymphocytes and Th1/Th2 cytokine secretion in children with aplastic anemia

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Regulatory T cells and CD20⁺B cells in pediatric very severe aplastic anemia: possible clinical markers for evaluating the therapeutic efficacy and prognosis