Changes of Subsets of DC 1 in the Bone Marrow of Severe Aplastic Anemia Patients.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 3712-3712
Author(s):  
Guangsheng He ◽  
Zhonghong Shao ◽  
De Pei Wu ◽  
Xiao Ma ◽  
Aining Sun
Keyword(s):  
Bone Marrow ◽  
Dendritic Cells ◽  
T Lymphocytes ◽  
Aplastic Anemia ◽  
Severe Aplastic Anemia ◽  
Stable Form ◽  
Th1 Cells ◽  
Th1 Cell ◽  
Cd8 Cells ◽  
Normal Controls

Abstract Objective To measure the changes of subsets of dendritic cells 1 (DC1) in the bone marrow of severe aplastic anemia (SAA) patients and evaluate the relationships between the CD11c+CD83+cells and Th1 cells, CD3+CD8+ cells or hematopoietic function. Methods By FACS, the quantity and ratio of CD11c+CD1a+ cells, CD11c+CD83+ cells, Th1 cells, and CD3+CD8+ cells in the bone marrow of SAA patients and normal controls were detected respectively. The relationships between CD3+CD8+ cells and Ret or ANC, between Th1 cells and CD3+CD8+ cells, Ret or ANC, between CD11c+CD83+ cells, and Th1 cells, CD3+CD8+ cells, Ret or ANC were evaluated. Results In normal control’s bone marrow, the percentages of Th1 cells, CD11c+CD1a+ cells, CD11c+CD83+ cells and ratio of CD11c+CD83+ /CD11c+CD1a+ was 0.42±0.30%, 0.38±0.29%, 0.37±0.32% and 1.07±0.10 respectively. In the untreated SAA patient’s bone marrow, they were 4.87±0.54%, 1.73±0.24%, 3.38±0.56% and 2.21±0.32 respectively, and increased markedly(p<0.01). In recovering SAA patient’s bone marrow, the percentages of Th1 cells, CD11c+CD1a+ cells and CD11c+CD83+ cells decreased significantly[0.53±0.22%, 0.61±0.23%, 0.65±0.22%, respectively (p<0.01)]. The ratio of CD11c+CD83+/CD11c+ CD1a+ of recovering SAA patients was 1.37±0.25 which was similar to that of normal controls (p>0.05). The percentages of CD3+CD8+ cells of untreated SAA patients was 32.32±10.22%, and that of recovering SAA patients decreased to 13.67%±5.24 significantly (p<0.01). The percentages of CD3+CD8+ cells of SAA patients were correlated to their Ret and ANC (P<0.05) negatively. Their Th1 cell percentages were correlated to their CD3+CD8+ cells positively (P<0.01), but to their Ret and ANC negatively(p<0.01). SAA patient’s CD11c+CD83+ cell percentages were correlated to their Th1 cell and CD3+CD8+ cells positively (P<0.01, P<0.05), but to their Ret and ANC negatively(p<0.01). Conclusion Both immature DC1 and activated DC1 increased in the bone marrow of SAA patients, and the balance of subsets of DC1 shifted from stable form to active one, which might promote Th0 cells to polarize to Th1 cells, then cause the over-function of T lymphocytes and hematopoietic failure in SAA.

In Vitro Study of the Function of Dendritic Cells on Stimulating T Lymphocytes Proliferation in Severe Aplastic Anemia

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4919-4919
Author(s):  
Zonghong Shao ◽  
Jun Wang ◽  
Rong Fu ◽  
Lijuan Li ◽  
Hui Liu ◽  
...  
Keyword(s):  
Growth Rate ◽  
Dendritic Cells ◽  
T Lymphocytes ◽  
Aplastic Anemia ◽  
Mononuclear Cells ◽  
Statistical Significance ◽  
In Vitro Study ◽  
Severe Aplastic Anemia ◽  
Normal Controls

Abstract Objective To investigate the function of dendritic cells (DCs) in severe aplastic anemia (SAA). Methods Fifteen untreated patients, 10 recovered patients with SAA and 12 normal controls were enrolled in this study. Their mDCs were induced from their bone marrow mononuclear cells with rhIL-4, rhGM-CSF and rhTNF in vitro. Then mDCs were co-cultured with allogenic lymphocytes (mixture lymphocyte reaction, MLR). The growth rate of lymphocyte was measured by MTT colorimetry and the concentrations of IL-12 and IFNγ in MLR supernatant were measured by ELISA. The correlation between the growth rate and the concentration of IL-12 or IFNγ was analyzed. Results When mDCs and lymphocytes were co-cultured at the ratio of 1:50, the growth rate of lymphocytes stimulated with the mDCs from untreated cases was (322.13±171.07)%, which was higher than those stimulated with the mDCs from recovered and controls [(180.90±79.12)%, (192.25±91.93)%] (P&lt;0.05). There was no statistical significance between the growth rates of lymphocytes stimulated with the mDCs from the recovered and controls (P&gt;0.05). The mDCs of 8 recovered cases and 4 controls were co-cultured with allogenic lymphocytes at the ratio of 1:100, 1:50, 1:20 and 1:10, but no statistical significance was found between two groups at each ratio (P&gt;0.05). Cross MLR showed only untreated cases versus normal had statistical significance (P&lt;0.05). The concentrations of IL-12 and IFNγ in MLR supernatant of untreated cases were higher than those of the recovered or controls (P&lt;0.05), but there was no statistical significance between the recovered and controls (P&gt;0.05). The concentration of IL-12 in MLR supernatant correlated positively with the growth rate of lymphocyte (r = 0.529,P=0.001), which was also positively correlated with the concentration of IFNγ (r = 0.381,P=0.024). Conclusion The function of mDCs to stimulate T lymphocytes proliferation by secretingt IL-12 in SAA was enhanced, which might play an important role in the immunopathogenesis of SAA.

scholarly journals PKM2 Is Required to Activate Myeloid Dendritic Cells from Patients with Severe Aplastic Anemia

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Chunyan Liu ◽  
Mengying Zheng ◽  
Ting Wang ◽  
Huijuan Jiang ◽  
Rong Fu ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Aplastic Anemia ◽  
Immune Status ◽  
Bone Marrow Failure ◽  
Severe Aplastic Anemia ◽  
Myeloid Dendritic Cells ◽  
Protein Levels ◽  
Immune Mediated ◽  
Normal Controls

Severe aplastic anemia (SAA) is an autoimmune disease in which bone marrow failure is mediated by activated myeloid dendritic cells (mDCs) and T lymphocytes. Recent research has identified a strong immunomodulatory effect of pyruvate kinase M2 (PKM2) on dendritic cells in immune-mediated diseases. In this study, we aimed to explore the role of PKM2 in the activation of mDCs in SAA. We observed conspicuously higher levels of PKM2 in mDCs from SAA patients compared to normal controls at both the gene and protein levels. Concurrently, we unexpectedly discovered that after the mDC-specific downregulation of PKM2, mDCs from patients with SAA exhibited weakened phagocytic activity and significantly decreased and shortened dendrites relative to their counterparts from normal controls. The expression levels of the costimulatory molecules CD86 and CD80 were also reduced on mDCs. Our results also suggested that PKM2 knockdown in mDCs reduced the abilities of these cells to promote the activation of CD8+ T cells (CTLs), leading to the decreased secretion of cytotoxic factors by the latter cell type. These findings demonstrate that mDC activation requires an elevated intrinsic PKM2 level and that PKM2 improves the immune status of patients with SAA by enhancing the functions of mDCs and, consequently, CTLs.

scholarly journals Aplastic anemia in China

2018 ◽  
Vol 6 (3) ◽  
pp. 134-137 ◽  
Author(s):  
Chunyan Liu ◽  
Zonghong Shao
Keyword(s):  
Bone Marrow ◽  
Autoimmune Disease ◽  
T Lymphocytes ◽  
Aplastic Anemia ◽  
Therapeutic Effect ◽  
Severe Aplastic Anemia ◽  
Hematologic Disease ◽  
Great Progress ◽  
Better Than

Abstract Aplastic anemia (AA) is a hematologic disease characterized by pancytopenia. Up to now, severe aplastic anemia (SAA) has been recognized by international and domestic scholars as an autoimmune disease with bone marrow (BM) failure mediated by the hyperfunctional T lymphocytes. The incidence of AA is more in China compared with other countries. In the recent years, both the pathogenesis and treatment of AA have made a great progress in our country. Thus, the therapeutic effect of AA was much better than before. Here, we conclude the researches of AA in China.

Quantity and Functional Changes of Subsets of Th Cells in the Bone Marrow of Severe Aplastic Anemia Patients.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 3711-3711
Author(s):  
Guangsheng He ◽  
Zhonghong Shao ◽  
De Pei Wu ◽  
Xiao Ma ◽  
Aining Sun
Keyword(s):  
Bone Marrow ◽  
Active Phase ◽  
Serum Levels ◽  
Recovery Phase ◽  
Th2 Cells ◽  
Th1 Cells ◽  
Functional Changes ◽  
Cd8 Cells ◽  
Tnf Α ◽  
Normal Controls

Abstract Objective To evaluate the quantity and functional changes of subsets of Th cells in the bone marrow of severe aplastic anemia (SAA) patients and the relationship between these changes and the patient hematopoietic function. Methods By FACS, the quantity and ratio of Th1 cells and Th2 cells, the percentage of CD3+CD8+ cells in the bone marrow were detected in 24 patients with SAA at active phase, 15 patients with SAA at recovery phase, and 16 normal controls respectively. By radioimmunoassay, the levels of cytokines of Th1 type (TNF-α), or Th2 type (IL-4) in the serum of 20 patients with SAA at active phase, 12 patients with SAA at recovery phase, 16 normal controls were measured respectively. The relationships between CD3+CD8+ cells, TNF-α and Ret, ANC were evaluated; the relationships between Th1 cells and CD3+CD8+ cells, TNF-α or Ret, ANC were evaluated; the relationships between IL-4, balance of Th1/Th2 and Ret, ANC were also evaluated. Results The percent of Th1 cells, Th2 cells, and ratio of Th1/Th2 in bone marrow of patients with SAA at active phase was: 4.87±2.64%, 0.41±0.26%, 21.22±5.07, were higher than those of normal controls: 0.42±0.30% (p<0.01), 0.24±0.17% (p<0.05), 1.57±0.93(p<0.01) respectively, and all of these decreased to normal levels at recovery phase (p>0.05); the percent of CD3+CD8+ cells decreased from 32.32±18.69% at active phase to 13.76±2.96% at recovery phase significantly (p<0.01); the serum levels of TNF-α, IL-4 at active phase was 4.29±3.15ng/ml and 1.24±0.73 ng/ml respectively, higher than those of normal controls(1.21±1.16 ng/ml, 1.18±0.97 ng/ml), but only the difference of TNF-α was significant (p<0.01); in recovery SAA patients, the serum levels of TNF-α significantly decreased to 1.46±1.41 ng/ml (p<0.01), and the levels of IL-4 increased continually markedly to 3.05±1.94 ng/ml; the CD3+CD8+ cells and TNF-α of patients correlated with Ret (p<0.05;p<0.05) and ANC (p<0.05;p<0.05) negatively, Th1 cells correlated with CD3+CD8+ cells and TNF-α positively (p<0.01;p<0.05), the Ret and ANC negatively(p<0.01;p<0.01), IL-4 and the balance of Th1/Th2 correlated with Ret and ANC positively (p<0.05;p<0.01) (p<0.01;p<0.01). Conclusion The formation of bone marrow failure in SAA might be caused not only by the increase of Th1 cells, Th1 type effective cells and cytokines, but also by unsufficient compensation of Th2 cells and Th2 type cytokines, which shifted the balance of Th1/Th2 to Th1.

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

2020 ◽  
Vol 2020 ◽  
pp. 1-10 ◽  
Author(s):  
Mengying Zheng ◽  
Bingnan Liu ◽  
Yuanyuan Shao ◽  
Luogang Hua ◽  
Rong Fu ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Mouse Model ◽  
Cyclosporin A ◽  
Aplastic Anemia ◽  
Survival Rates ◽  
Severe Aplastic Anemia ◽  
High Survival ◽  
Myeloid Dendritic Cells ◽  
Cd8 Cells

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.

scholarly journals Upregulated Expression of Profilin1 on Dendritic Cells in Patients With Severe Aplastic Anemia

2021 ◽  
Vol 12 ◽  
Author(s):  
Hong Yu ◽  
Yang Zhao ◽  
Xiaofeng Pan ◽  
Chunyan Liu ◽  
Rong Fu
Keyword(s):  
Bone Marrow ◽  
Dendritic Cells ◽  
Aplastic Anemia ◽  
Bone Marrow Failure ◽  
Cell Movement ◽  
Severe Aplastic Anemia ◽  
Myeloid Dendritic Cells ◽  
Life Threatening ◽  
Movement Ability ◽  
Antigen Presenting

Severe aplastic anemia (SAA) is a life-threatening form of bone marrow failure that is associated with very high mortality. Dendritic cells (DCs) are antigen presenting cells (APCs) with powerful movement ability, which is an important factor affecting immune function. The expression of profilin1 (Pfn1) plays an important role in the regulation of cell movement ability. We detected the expression of Pfn1 mRNA in the bone marrow (BM) myeloid dendritic cells (mDCs) from patients with SAA using RT-PCR. Next, we examined Pfn1 expression on mDCs using flow cytometry (FCM). We also assessed the relationship between Pfn1 expression and cytokine levels. Our data showed increased Pfn1 mRNA expression in patients with SAA. The expression of Pfn1 in BM mDCs increased in SAA patients. The expression of Pfn1 on mDCs and cytokines (TNF-α and IFN-γ) were positively correlated in the serum of untreated patients with SAA. Taken together, we found that the expression of Pfn1 on mDCs of SAA patients increased, which may affect the function of mDCs. Profilin 1 may be involved in the immunopathogenesis of SAA.

Research of Subset and Function of Th Cells in Bone Marrow of Myelodysplastic Syndrome Patients.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 4913-4913
Author(s):  
Xiuli Wang ◽  
De Pei Wu ◽  
Guangsheng He ◽  
Miao Miao ◽  
Aining Sun
Keyword(s):  
Bone Marrow ◽  
T Cell ◽  
T Lymphocytes ◽  
Tumor Cell ◽  
Cd4 T Cell ◽  
Th2 Cells ◽  
Neoplastic Disease ◽  
Th1 Cells ◽  
Blast Cells ◽  
Normal Controls

Abstract Objective To study the quantity and ratio of Th1, Th2 cells in the bone marrow of patients with MDS;The tumor burden that Th1 cells bear in the patients with MDS. Evaluation of the correlation between the ratio of the blast cells and the number of the Th1 cells in the bone marrow in the patients with MDS. Methods By FACS, the quantity and ratio of IFN-γ producing CD4+ T cell (Th1) and IL-4 producing CD4+ T cell (Th2) cells in the bone marrow were detected in 21 patients with MDS,18 normal controls and 13 patients with SAA respectively;The karyotypes of 18 patients with MDS and 15 normal controls were detected, The burden,(the number of the cells with anormal karyotypes /the number of all the detected cells) that Th1 cells bear in the patients with MDS and that in normal controls were analyzed;The correlation between the ratio of the blast cells in the bone marrow and the number of the Th1 cells in the patients with MDS was also analyzed. Results The percentages of Th1 cells and Th2 cells and ratio of Th1/Th2 in the bone marrow of normal controls were: (0.48±0.10)%,(0.24±0.19)%,2.31±0.76 respectively, while those of the patients with MDS were (0.36±0.11)%,(0.76±0.35)% and 0.51±0.13. The percentage of Th1 cells of patients with MDS was reduced and the ratio of Th1/Th2 of them was significantly lower than that of normal controls(p&lt;0.01); Those of the patients with SAA were: (4.75±0.49)%,(0.40±0.28)%,26.5±8.79 respectively, their Th1 cells and ratio of Th1/Th2 were markedly higher than those of normal controls (P&lt;0.01); In all of the 15 normal controls the karyotypes were normal, and tumor cell burden was zero, While in the group of MDS, tumor cell burden, (the number of the cells with anormal karyotype /the number of all detected cells) was (50.00±0.10)%. The MDS patients’ ratio of tumor cell burden / Th1 cells (1.72±1.23) was much higher than that of normal controls whose burden was zero;The lower ratio of the Th1 cells in the bone marrow of the patients with MDS and the AML which converts from MDS, the higher percentage of the blast cells, they were negatively correlated (r=−0.563, p&lt;0.01). Conclusion The immune function of T lymphocytes in MDS is abnormal: the balance between Th1 and Th2 cells is broken. Th1 cell, the most important element for antitumorigenesis, is decreased. Comparing with the burden of the malignant clone, the number of Th1 cells of the patients with MDS is overwhelmingly scarce. With descending of the number of Th1 cells in the bone marrow of the patients with MDS, the number of the blast cells contrarily grows. MDS is a heterogeneous group of neoplastic disease accompanied with hypofunction of the T lymphocytes mediating immune surveillance. All these hint that during the treat of clearing the malignant clone of MDS, enhancement of the T cell fuction should been done.

Quantitative Changes of T Helper Cell 3 and CD4+CD25+T Regulator Cells in Peripheral Blood and the Serum Levels of TGF-β1 of the Patients with Severe Aplastic Anemia.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3752-3752
Author(s):  
Zonghong Shao ◽  
Meifeng Tu ◽  
Hong Liu ◽  
Guangsheng He ◽  
Jun Shi ◽  
...  
Keyword(s):  
Aplastic Anemia ◽  
Peripheral Blood ◽  
Active Phase ◽  
Serum Levels ◽  
Recovery Phase ◽  
Severe Aplastic Anemia ◽  
Enzyme Linked Immunosorbent Assay ◽  
Cd8 Cells ◽  
Normal Controls ◽  
Tgf Β1

Abstract Objective To probe the mechanism of autoimmune intolerance in severe aplastic anemia (SAA), the percentages of Th3 cells and CD4+CD25+T regulator cells in peripheral blood and the serum levels of TGF-β1 of SAA patients at disease active and recovery phases and those of normal controls were measured. Methods By FACS, the quantity of TGF-β producing CD4+ T cells (Th3)in the peripheral blood of 20 patients with SAA at active phase,10 patients with SAA at recovery phase and 12 normal controls were detected respectively. By FACS, the percentages of CD4+CD25+T regulator cells in peripheral blood of 12 patients with SAA at active phase, 9 non-recuperated patients after IST, 6 patients at recovery phase and 12 normal controls were counted, and its correlation with the percentages of CD3+CD4+, CD3+CD8+ cells and the ratio of CD3+CD4+to CD3+CD8+ were analyzed. By enzyme linked immunosorbent assay (ELISA), the level of TGF-β1 in serum of 25 patients with SAA and 13 normal controls were measured respectively and its correlation with peripheral platelets counts was analyzed. Results The percentages of Th3 cells, CD8+TGF-β1+cells and the ratio of Th3/CD8+TGF-β1+in peripheral blood of controls were(5.10±3.16)%,(4.93±3.36)%,1.20±0.67 respectively, and those of the patients with SAA at active phase were(1.33±0.91)%,(1.72±1.07)%,1.00±1.13 respectively. Th3 cells and CD8+TGF-β1+of SAA patients were significantly lower than those of normal controls(p<0.01, p<0.05). The aforementioned merits of SAA patients at recovery phase increased to(2.19±0.66)%,(2.07±1.03)%,1.71±1.64 respectively, but the percentages of Th3 cells and CD8+TGF-β1+were still significant lower than those of normal controls (P<0.05). The percentage of Th3 cells decreased in the SAA patients, which broke the autoimmune tolerance in SAA. The percentage of CD4+CD25+T regulator cells in peripheral blood of controls was(8.25±6.78)%, and that of SAA patients was (3.32±2.80)%, which was significantly lower than that of normal controls. The percentages of CD4+CD25+T regulator cells of 9 non-recuperated patients and 10 patients at recovery phase increased to(7.09±5.52)% and(7.49±4.03)% respectively, which were not significantly different from those of normal controls. The percentage of CD4+CD25+T regulator cells of SAA patients was related to the percentage of CD3+CD4+ cells and the ratio of CD3+CD4+and CD3+CD8+ positively, but related to the percentage of CD3+CD8+cells negatively. The percentage of CD4+CD25+T regulate cells decreased in the SAA patients, which broke the autoimmune tolerance in SAA. The level of TGF-β1 in plasma of normal controls was (11.06±1.75) ng/ml. That of SAA patients was (2.49±2.55) ng/ml, which was markedly lower than that of normal controls(p<0.001). The level of TGF-β1 in plasma of SAA patients was related to the percentage of Th3 cells and the platelet counts positively (p<0.05, p<0.001). The level of TGF-β1 in the plasma of SAA patients decreased. Conclusion The percentages of Th3 and CD4+CD25+T regulate cells in the peripheral blood, and the level of TGF-β1 in plasma of the SAA patients decreased, which broke the autoimmune tolerance in SAA.

scholarly journals Pyruvate Kinase M2 Regulates Hif-1alpha Activity in Myeloid Dendritic Cells from Patients with Severe Aplastic Anemia

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 1109-1109
Author(s):  
Xiaowei Liang ◽  
Lijie Zeng ◽  
Xiaoyu Zhao ◽  
Chunyan Liu ◽  
Zonghong Shao ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Dendritic Cells ◽  
Aplastic Anemia ◽  
Mrna Expression ◽  
Immune Cells ◽  
Expression Level ◽  
Control Group ◽  
Mrna Expression Level ◽  
Myeloid Dendritic Cells ◽  
Normal Controls

Abstract Hypoxia-inducible factor 1 (HIF-1) is a nuclear protein with transcriptional activity. HIF-1 can be activated by immune cells exposed to hypoxia and regulate glycolysis. In this regulation, pyruvate kinase M2 (PKM2), a key enzyme in the cell glycolytic pathway, is an important regulatory site. Our previous studies suggest that PKM expression is increased in myeloid dendritic cells (mDCs) in SAA patients. Therefore, we investigated the expression level of HIF-1α in mDCs and its interaction with PKM2 in SAA patients. The HIF-1α expression of mRNA and protein on mDCs in SAA untreated patients was significantly higher than that in SAA remission patients and normal controls. In the SAA patients, the HIF-1α expression on mDCs was positively correlated with the numbers of mDCs (p &lt; 0.01), CD80+mDC/mDC (r = 0.689, p &lt; 0.01), and CD86+mDC/mDC in PB (p &lt; 0.05). In SAA patients, the HIF-1α expression on mDCs was negatively correlated with the CD4+T/CD8+T ratio in peripheral blood (PB) (p &lt; 0.05), the percentage of granulocytoid and erythroid cells in bone marrow (p &lt; 0.05), the WBC count in PB (p &lt; 0.05), ANC in PB (p &lt; 0.05), and the percentage of Rets in the PB (p &lt; 0.05); was positively correlated with the percentage of lymphoid cells in bone marrow(p &lt; 0.05); and was not statistically correlated with the megakaryocyte number in bone marrow, absolute PBL count, HGB in PB, absolute Ret count in PB, or PLT count in PB. In the correlation analysis we observed that there was a positively correlation between HIF-1α and PKM2 expression on mDCs in SAA patients (p &lt; 0.001). To evaluate whether there is a mutual adjustment relationship between HIF-1α and PKM2, we successfully reduced PKM2 gene expression in this cell population via siRNA transfection. This process resulted in significantly lower levels of PKM2 protein expression relative to cells transfected with siControl which were evaluated by western blotting. We observed that the relative expression levels of HIF-1α mRNA in mDCs transfected with PKM2 siRNA was lower than siControl group（P&lt; 0.01）. Conclusions  In this study, we found that untreated patients with SAA had higher HIF-1α expression on mDCs compared with recovering SAA patients and normal controls. The expression of HIF-1α was correlated with the number and function in mDCs and the severity of pancytopenia of SAA. The results indicated that the mRNA expression level of HIF-1α in mDC of SAA patients at the onset was significantly higher than that of the remission group and the control group, and was significantly positively correlated with the expression of PKM2. The mRNA expression level of HIF-1α in mDC of SAA patients at the onset was significantly higher than that of the remission group and the control group, and was significantly positively correlated with the expression of PKM2. The above experimental results confirmed that HIF-1α plays an important role in the abnormal immune response in patients with severe aplastic anemia, mainly by regulating the activity of PKM2 and thereby affecting the energy metabolism in immune cells. Disclosures No relevant conflicts of interest to declare.

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