1.Increased receptor activator of nuclear factor kappa B ligand expressed on B10 cells in rheumatoid arthritis.
Hong Jiang LIU ; Xiao Feng GUO ; Fan Lei HU ; Cui Ping YAN ; Xiang Jun CUI ; Xue Liang YAN ; Zhan Guo LI ; Yuan JIA ; Shu Lin SONG
Journal of Peking University(Health Sciences) 2018;50(6):968-974
OBJECTIVE:
To detect receptor activator of nuclear factor kappa B ligand (RANKL) expressed on B10 cells in rheumatoid arthritis (RA) and to evaluate the correlation between RANKL-producing B10 cells in RA and clinical features and laboratory parameters, trying to reveal the possible role of B10 cells in the pathogenesis of RA and the potential mechanism of impaired immunosuppressive capacities.
METHODS:
25 RA patients and 20 healthy volunteers were enrolled. These RA patients did not received treatment with glucocorticoids, disease-modifying anti-rheumatic drug and biologics during the recent half of a year. The levels of RANKL-producing B10 cells were measured by flow cytometry (FCM) and polymerase chain reaction (PCR). The correlation between the frequencies of RANKL-producing B10 cells in RA and clinical data, laboratory parameters were analyzed. The role of tumor necrosis factor α (TNF-α) and interleukin 1β (IL-1β) in inducing RANKL expression in B10 cells was evaluated by in vitro stimulation assay. Independent samples t test, Pearson and Spearman correlation were used for statistical analysis.
RESULTS:
B10 cells were capable of producing RANKL at a low level in health controls. The frequencies of RANKL-producing B10 cells were markedly higher in RA patients than in health controls (3.65%±1.59% vs. 2.25%±0.68%, P<0.01). The frequencies of these cells correlated positively with RA tender joint counts, swollen joint counts and disease activity score in 28 joints (DAS28) (r=0.479, P=0.035; r=0.519, P=0.008; r=0.526, P=0.019). However, no correlation was found between these cells and RA patient age, disease duration, or the levels of erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), rheumatoid factor (RF) and anti-citrullinated peptide antibody (ACPA). After in vitro stimulation by TNF-α, but not IL-1β, B10 cells isolated from healthy donors demonstrated fundamentally upregulated expression of RANKL.
CONCLUSION
Our studies showed the frequencies of RANKL-producing B10 cells were markedly higher in RA patients, and their frequencies were positively correlated with RA tender joint counts, swollen joint counts and DAS28. These findings suggested that B10 cells might be involved in RA bone destruction.
Antirheumatic Agents
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Arthritis, Rheumatoid/metabolism*
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Autoantibodies/metabolism*
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B-Lymphocytes, Regulatory/metabolism*
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Humans
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RANK Ligand/metabolism*
;
Rheumatoid Factor
2.Inhibitory function of Tregs via soluble FGL2 in chronic hepatitis B.
Li XU ; Daofeng YANG ; Yanlin LIU ; Di WU ; Xiaojing WANG ; Qin NING
Journal of Huazhong University of Science and Technology (Medical Sciences) 2012;32(4):540-545
CD4(+)CD25(+)CD127(dim/-) regulatory T cells (Tregs) have been implicated in suppressing T cell immune responses to hepatitis B virus (HBV), but the inhibition mechanism has not being clear yet. This study investigated the effects of soluble FGL2 (sFGL2) secreted by Tregs on immune suppression in chronic HBV-infected patients. We verified that sFGL2 protein and mRNA were highly expressed in Tregs. The separated Tregs by using magnetic beads from peripheral blood mononuclear cells (PBMCs) in 20 patients with chronic hepatitis B were co-cultured with PBMCs at a ratio of 1:3 with anti-CD3 stimulating antibody or FGL2 blocking antibody. The proliferation index of CD8(+)T cells after blocking FGL2 was higher than that in blank group (3.58±0.18 vs. 3.28±0.17, P=0.034) in 18 of 20 samples, and lower than that in CD3 stimulation group (3.82±0.19, P=0.026) in 16 of 20 samples. The IFN-γ secreted in the mixed culture in the absence of Tregs was higher than that in the culture in the presence of Tregs, but it could be abolished by FGL2 blocking antibody. These results suggest that sFGL2 protein secreted by Tregs suppresses the proliferation and function of CD8(+) T cells in chronic hepatitis B.
CD8-Positive T-Lymphocytes
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immunology
;
metabolism
;
Cells, Cultured
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Fibrinogen
;
immunology
;
metabolism
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Hepatitis B, Chronic
;
immunology
;
metabolism
;
Humans
;
T-Lymphocytes, Regulatory
;
immunology
;
metabolism
3.Impacts of yishen jiangzhuo granule on B lymphocytes and regulatory T-lymphocytes in patients with chronic renal insufficiency.
Jing ZHENG ; Shang-zhong LIN ; Xue-lan CHEN
Chinese Journal of Integrated Traditional and Western Medicine 2011;31(1):37-40
<b>OBJECTIVEb>To explore the impacts of Yishen Jiangzhuo Granule (YJG) on peripheral blood B-cells and regulatory T-cells (Treg) in patients with chronic renal insufficiency (CRI).
<b>METHODSb>Fifty-three CRI patients were randomly assigned to two groups, the control group and the YJG group. Before and after treatment, the following parameters in blood were detected: the peripheral Treg, percentage (CD19+), activation rate (CD19+ CD69+) and apoptotic rate (AV) of B-lymphocyte by flow cytometry; cytokines (IL-6 and IL-10) by CBA stream protein analyzing system; high sensitivity C-reactive protein (hs-CRP) by scattering turbidimetric analysis; homocysteine (Hcy) by end-point method; hemoglobin (HGB) content by Beckman-Coulter hemo-analyser; blood contents of Ca, phosphate (P), blood urea nitrogen (BUN), creatinine (SCr) and plasma albumin (Alb) by automatic biochemical analyser; and urinary contents of creatinine (UCr) by inverse HPLC. Then the product of calcium-phosphate (Ca x P) was calculated based on blood contents of Ca2 and P and the clearance rate of endogenous creatinine (CCr) was calculated based on blood BUN and SCr.
<b>RESULTSb>After treatment CD19+ and CCr significantly increased (P < 0.01), but AV and SCr decreased in both groups (P < 0.01), with the changes in the YJG group were more significant than those in the control group (P < 0.05); levels of CD19+ CD69+, Treg, IL-6, IL-10, CRP, BUN, P and Ca x P showed no significant change (P > 0.05); levels of Ca2+, HGB and Alb increased as well as of Hcy in both groups (P < 0.05). Correlation analysis: There were negative correlation in CD19+ with AV and Hcy; Alb with AV and Hcy; CCr with CRP, SCr and BUN, while positive correlation existed in SCr with CRP and BUN; and CRP with BUN.
<b>CONCLUSIONSb>YJG can improve renal function, and delay the progress of renal failure, and it also shows the regulatory effect on B lymphocytes by lowering the apoptosis rate and improving the percentage of CD19+ in patients.
Adult ; Aged ; B-Lymphocytes ; metabolism ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Humans ; Kidney Failure, Chronic ; drug therapy ; metabolism ; Male ; Middle Aged ; Phytotherapy ; T-Lymphocytes, Regulatory ; metabolism
4.Unusual Suspects in the Development of Obesity-Induced Inflammation and Insulin Resistance: NK cells, iNKT cells, and ILCs.
Beatriz Dal Santo Francisco BONAMICHI ; Jongsoon LEE
Diabetes & Metabolism Journal 2017;41(4):229-250
The notion that obesity-induced inflammation mediates the development of insulin resistance in animal models and humans has been gaining strong support. It has also been shown that immune cells in local tissues, in particular in visceral adipose tissue, play a major role in the regulation of obesity-induced inflammation. Specifically, obesity increases the numbers and activation of proinflammatory immune cells, including M1 macrophages, neutrophils, Th1 CD4 T cells, and CD8 T cells, while simultaneously suppressing anti-inflammatory cells such as M2 macrophages, CD4 regulatory T cells, regulatory B cells, and eosinophils. Recently, however, new cell types have been shown to participate in the development of obesity-induced inflammation and insulin resistance. Some of these cell types also appear to regulate obesity. These cells are natural killer (NK) cells and innate lymphoid cells (ILCs), which are closely related, and invariant natural killer T (iNKT) cells. It should be noted that, although iNKT cells resemble NK cells in name, they are actually a completely different cell type in terms of their development and functions in immunity and metabolism. In this review, we will focus on the roles that these relatively new players in the metabolism field play in obesity-induced insulin resistance and the regulation of obesity.
B-Lymphocytes, Regulatory
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Diabetes Mellitus, Type 2
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Eosinophils
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Humans
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Inflammation*
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Insulin Resistance*
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Insulin*
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Intra-Abdominal Fat
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Killer Cells, Natural*
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Lymphocytes
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Macrophages
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Metabolism
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Models, Animal
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Natural Killer T-Cells*
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Neutrophils
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Obesity
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T-Lymphocytes
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T-Lymphocytes, Regulatory
5.Progress in the Treatment of Adult Langerhans Cell Histiocytosis --Review.
Zi-Zhu TIAN ; Ya-Juan CUI ; Hong-Ling PENG
Journal of Experimental Hematology 2022;30(3):970-974
Langerhans cell histiocytosis (LCH) is a rare proliferative disease dominated by the proliferation of Langerhans cells, which is inflammatory myeloid neoplasms. Its clinical manifestations are variable, occurring at any age and at any site, and it is rarer in adults than in children. The gold standard for diagnosis is histopathological biopsy. Due to the rarity of adult LCH and the heterogeneity of this disease, treatment of adult LCH should be developed according to the extent of the disease and risk stratification. With the discovery of MAPK, PI3K and c-KIT signaling pathway activation, especially BRAF V600E and MAP2K1 mutations, targeted therapy has become a hot spot for therapeutic research. Meanwhile, the discovery of high expression of M2-polarized macrophages and Foxp3+ regulatory T cells (Treg) in LCH has provided an important basis for the immunotherapy. In this article, we will focus on reviewing the latest research progress in the treatment of adult LCH in recent years, and provide a reference for clinical research on the treatment of adult LCH patients.
Adult
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Child
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Histiocytosis, Langerhans-Cell/therapy*
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Humans
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Mutation
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Proto-Oncogene Proteins B-raf/metabolism*
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Signal Transduction
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T-Lymphocytes, Regulatory/pathology*
6.Research progress on B lymphocyte-induced maturation protein 1 and its relationship with the development of lymphoma.
Journal of Experimental Hematology 2013;21(6):1623-1626
Many studies show that as a transcription factor, B lymphocyte-induced maturation protein 1 (Blimp 1) is the master regulator of plasma-cell differentiation. The abnormality of Blimp 1 plays an important part in the genesis and development of lymphoma. This review introduces and summarizes Blimp 1's protein structure and functions, its role in B cell differentiation, its main target genes and the mechanism of its transcriptional repressor activity. Besides, the relationship between Blimp 1 gene mutation or Blimp 1 protein expression reduction and the development of DLBCL is preliminary summaried.
B-Cell Maturation Antigen
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genetics
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B-Lymphocytes
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Cell Differentiation
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Humans
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Lymphoma, Large B-Cell, Diffuse
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Positive Regulatory Domain I-Binding Factor 1
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Repressor Proteins
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metabolism
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Transcription Factors
7.Colocalization of Interferon Regulatory Factor 7 (IRF7) with Latent Membrane Protein 1 (LMP1) of Epstein-Barr Virus.
Journal of Korean Medical Science 2006;21(3):379-384
Interferon regulatory factor 7 (IRF7) is one of the transcriptional factors for the activation of type I Interferon (IFN) genes. It is known that IRF7 and the latent membrane protein 1 (LMP1) of Epstein-Barr virus (EBV) are highly expressed in EBV type III latency cells, and LMP1 induces mRNA expression of IRF7. In this study, the expression pattern of endogenous IRF7 was observed in several B cell lines with or without EBV infection by immunofluorescence staining. IRF7 was localized in the cytoplasm of EBV-negative B cells and EBV type I latency B cell lines. However, IRF7 was located both in the cytoplasm and nucleus of EBV type III latency cell lines. In the Jijoye cell (type III latency cell), IRF7 was colocalized with LMP1 in the cytoplasm in a capping configuration, and their interaction was confirmed by co-immunoprecipitation of LMP1 and IRF7. This colocalization was confirmed by co-transfection of IRF7 and LMP1 plasmids in EBV-negative B cells. These results suggest that the IRF7 and LMP1 interact with each other, and this may relate to the mechanism whereby LMP1 exerts functional effects in B-lymphocytes.
Viral Matrix Proteins/*biosynthesis/metabolism
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Trans-Activation (Genetics)
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Signal Transduction
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RNA, Messenger/metabolism
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Plasmids/metabolism
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Microscopy, Fluorescence
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Interferon Regulatory Factor-7/*biosynthesis
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Immunoprecipitation
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Humans
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Herpesvirus 4, Human/metabolism
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*Gene Expression Regulation
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Cytoplasm/metabolism
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Cell Line, Tumor
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B-Lymphocytes/metabolism/virology
8.Dynamic expression of PD-1 in HBV-specific cytotoxic T lymphocytes correlates with memory T-cell development in acute hepatitis B patients.
Lan-lan GU ; Bin XU ; Ji-yuan ZHANG ; Zheng ZHANG ; Fu-sheng WANG
Chinese Journal of Hepatology 2008;16(9):649-653
<b>OBJECTIVESb>Programmed death-1 (PD-1) up-regulation impairs virus-specific CD8+ T-cell responses during chronic viral infection. Whether PD-1 expression influences the virus-specific CD8+ T cells in humans with acute viral infection remains largely undefined. This study aims to characterize the PD-1 expression during acute hepatitis B (AHB), and further addresses the association between the PD-1 dynamics and memory T-cell formation during acute HBV infection.
<b>METHODSb>Peripheral HBV-specific CD8+ T cells from 11 HLA-A2-positive AHB patients were longitudinally quantitatively analyzed, and PD-1, memory markers CCR7, CD45RA and CD127 and activation marker CD38 on HBV-specific CD8+ T cells were measured using flow cytometric assay. Serum ALT, HBsAg, HBsAb and HBV-DNA levels were evaluated for each subject.
<b>RESULTSb>All 11 AHB patients examined had multiple pentamer-positive CD8+ T-cell responses in their early phase of HBV infection. Specifically, their PD-1 on pentamer-positive CD8+ T-cells was significantly up-regulated at the onset of their disease. Following their disease resolution, the dynamic decrease in PD-1 expression was found to correlate with the phenotypic development of memory CD8+ T cells, indicated by the increases in CCR7, CD45RA and CD127 and decrease in CD38.
<b>CONCLUSIONb>PD-1-mediated negative signaling may be closely associated with memory T-cell formation during acute self-limited hepatitis B.
Acute Disease ; Adult ; Antigens, CD ; metabolism ; Apoptosis Regulatory Proteins ; metabolism ; Female ; Hepatitis B ; immunology ; metabolism ; Humans ; Immunologic Memory ; Male ; Middle Aged ; Programmed Cell Death 1 Receptor ; T-Lymphocytes, Cytotoxic ; immunology ; metabolism ; Young Adult
9.Research of PD-1 expression in CD8+ T cell of peripheral blood with HBV-associated acute-on-chronic liver failure.
Xiao-Yan LIU ; Feng SHI ; Hong ZHAO ; Hui-Fen WANG
Chinese Journal of Experimental and Clinical Virology 2010;24(2):125-127
<b>OBJECTIVEb>To analyze PD-1 expression in CD8 + T cell of Peripheral blood with HBV-associated acute-on-chronic liver failure and effect on CD8+ T cell.
<b>METHODSb>We selected 60 patients with HBV-ACLF and collected their peripheral blood. We analyzed the expressions of PD-1, CD95, perforin, granzyme A, granzyme B, CD107a on CD8+ T lymphocytes and the expression of PD-L1 on monocytes peripheral blood by using flow cytometry. 15 liver cirrhosis patients( LC) and 15 healthy individuals( HC) are control groups.
<b>RESULTb>PD-1 expression was (1) The PD-1 expression in HBV-ACLF patients was significantly elevated compared with those in HC and lower in improved group than that in invalid group and death group (P < 0.05) and increased from prophase, metaphase to advanced stage (P < 0.05). Moreover, (2) PD-L1 expression on monocytes was positively correlated with disease progression. (P < 0.05). (3) Both PD-1 and CD95 expressions were higher in dead group than those in improved and non-improved groups. Perforin, granzymes and CD107a expressions on CD8+ T cells significantly increased in dead group compared with those in improved and non-improved groups (P < 0.05). However, PD-1 expressions on these cells were lower, compared with normal persons.
<b>CONCLUSIONSb>The expression of PD-1 and PD-L1 in HBV-ACLF patients was positively correlated with disease progression. The elevated PD-1 expression promoted apoptosis of CD8+ T cells. For HBV-ACLF patients, the PD-1 expression on effector CD8+ T cells was lower than those in other CD8+ T cells, which maybe accounted for the failure to controlling immune injury in liver.
Antigens, CD ; metabolism ; Apoptosis Regulatory Proteins ; metabolism ; CD8-Positive T-Lymphocytes ; metabolism ; Female ; Flow Cytometry ; Hepatitis B virus ; pathogenicity ; Humans ; Liver Failure, Acute ; immunology ; metabolism ; virology ; Male ; Middle Aged ; Programmed Cell Death 1 Receptor
10.B cell-associated immune profiles in patients with end-stage renal disease (ESRD).
Kyoung Woon KIM ; Byung Ha CHUNG ; Eun Joo JEON ; Bo Mi KIM ; Bum Soon CHOI ; Cheol Whee PARK ; Yong Soo KIM ; Seok Goo CHO ; Mi La CHO ; Chul Woo YANG
Experimental & Molecular Medicine 2012;44(8):465-472
Most of the previous studies on immune dysregulation in end-stage renal disease (ESRD) have focused on T cell immunity. We investigated B cell subpopulations in ESRD patients and the effect of hemodialysis (HD) on B cell-associated immune profiles in these patients. Forty-four ESRD [maintenance HD patients (n = 27) and pre-dialysis patients (n = 17)] and 27 healthy volunteers were included in this study. We determined the percentage of B cell subtypes, such as mature and immature B cells, memory B cells, and interleukin (IL)-10+ cells, as well as B cell-producing cytokines (IL-10, IL-4 and IL-21) by florescent activated cell sorting (FACS). B cell-associated gene expression was examined using real-time PCR and B cell producing cytokines (IL-10, IL-4 and IL-21) were determined using an enzyme-linked immunosorbent assay (ELISA). The percentage of total B cells and mature B cells did not differ significantly among the three groups. The percentages of memory B cells were significantly higher in the pre-dialysis group than in the HD group (P < 0.01), but the percentage of immature B cells was significantly lower in the pre-dialysis group than in the other groups. The percentages of IL-10-expressing cells that were CD19+ or immature B cells did not differ significantly (P > 0.05) between the two subgroups within the ESRD group, but the serum IL-10 concentration was significantly lower in the pre-dialysis group (P < 0.01). The results of this study demonstrate significantly altered B cell-associated immunity. Specifically, an imbalance of immature and memory B cells in ESRD patients was observed, with this finding predominating in pre-dialysis patients.
Adaptor Proteins, Signal Transducing/genetics
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Adult
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Antigens, CD19/metabolism
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B-Lymphocyte Subsets/immunology/metabolism
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B-Lymphocytes/*immunology/metabolism
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Cytokines/biosynthesis
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Female
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Humans
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Immunophenotyping
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Interleukin-10/metabolism
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Kidney Failure, Chronic/*immunology/metabolism
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Leukocytes, Mononuclear/metabolism
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Male
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Middle Aged
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Proto-Oncogene Proteins/genetics
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T-Lymphocytes, Regulatory/immunology/metabolism