Rapid generation of maturationally synchronized human dendritic cells: contribution to the clinical efficacy of extracorporeal photochemotherapy.
Extracorporeal photochemotherapy (ECP) is widely used to treat cutaneous T-cell lymphoma,graft-versus-host disease,and allografted organ rejection. Its clinical and experimental efficacy in cancer immunotherapy and autoreactive disorders suggests a novel mechanism. This study reveals that ECP induces a high percentage of processed monocytes to enter the antigen-presenting dendritic cell (DC) differentiation pathway,within a single day,without added cytokines,as determined by enhanced expression of relevant genes. The resulting DCs are capable of processing and presentation of exogenous and endogenous antigen and are largely maturationally synchronized,as assessed by the level of expression of costimulatory surface molecules. Principal component analysis of the ECP-induced monocyte transcriptome reveals that activation or suppression of more than 1100 genes produces a reproducible distinctive molecular signature,common to ECP-processed monocytes from normal subjects,and those from patients. Because ECP induces normal monocytes to enter the DC differentiation pathway,this phenomenon is independent of disease state. The efficiency with which ECP stimulates new functional DCs supports the possibility that these cells participate prominently in the clinical successes of the treatment. Appropriately modified by future advances,ECP may potentially offer a general source of therapeutic DCs.
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产品号#：
19059
19059RF
产品名：
EasySep™人单核细胞富集试剂盒
RoboSep™ 人单核细胞富集试剂盒含滤芯吸头
Merino A et al. (FEB 2011)
Journal of immunology (Baltimore,Md. : 1950) 186 3 1809--15
Senescent CD14+CD16+ monocytes exhibit proinflammatory and proatherosclerotic activity.
In elderly subjects and in patients with chronic inflammatory diseases,there is an increased subset of monocytes with a CD14(+)CD16(+) phenotype,whose origin and functional relevance has not been well characterized. In this study,we determined whether prolonged survival of human CD14(++)CD16(-) monocytes promotes the emergence of senescent cells,and we analyzed their molecular phenotypic and functional characteristics. We used an in vitro model to prolong the life span of healthy monocytes. We determined cell senescence,intracellular cytokine expression,ability to interact with endothelial cells,and APC activity. CD14(+)CD16(+) monocytes were senescent cells with shortened telomeres (215 ± 37 relative telomere length) versus CD14(++)CD16(-) cells (339 ± 44 relative telomere length; p textless 0.05) and increased expression of β-galactosidase (86.4 ± 16.4% versus 10.3 ± 7.5%,respectively; p = 0.002). CD14(+)CD16(+) monocytes exhibited features of activated cells that included expression of CD209,release of cytokines in response to low-intensity stimulus,and increased capacity to sustain lymphocyte proliferation. Finally,compared with CD14(++)CD16(-) cells,CD14(+)CD16(+) monocytes showed elevated expression of chemokine receptors and increased adhesion to endothelial cells (19.6 ± 8.1% versus 5.3 ± 4.1%; p = 0.033). In summary,our data indicated that the senescent CD14(+)CD16(+) monocytes are activated cells,with increased inflammatory activity and ability to interact with endothelial cells. Therefore,accumulation of senescent monocytes may explain,in part,the development of chronic inflammation and atherosclerosis in elderly subjects and in patients with chronic inflammatory diseases.
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产品号#：
19059
19059RF
产品名：
EasySep™人单核细胞富集试剂盒
RoboSep™ 人单核细胞富集试剂盒含滤芯吸头
Xu X et al. ( 2014)
The Journal of Immunology 193 8 4125--4136
IFN-Stimulated Gene LY6E in Monocytes Regulates the CD14/TLR4 Pathway but Inadequately Restrains the Hyperactivation of Monocytes during Chronic HIV-1 Infection
Owing to ongoing recognition of pathogen-associated molecular patterns,immune activation and upregulation of IFN-stimulated genes (ISGs) are sustained in the chronically infected host. Albeit most ISGs are important effectors for containing viral replication,some might exert compensatory immune suppression to limit pathological dysfunctions,although the mechanisms are not fully understood. In this study,we report that the ISG lymphocyte Ag 6 complex,locus E (LY6E) is a negative immune regulator of monocytes. LY6E in monocytes negatively modulated CD14 expression and subsequently dampened the responsiveness to LPS stimulation in vitro. In the setting of chronic HIV infection,the upregulation of LY6E was correlated with reduced CD14 level on monocytes; however,the immunosuppressive effect of LY6E was not adequate to remedy the hyperresponsiveness of activated monocytes. Taken together,the regulatory LY6E pathway in monocytes represents one of negative feedback mechanisms that counterbalance monocyte activation,which might be caused by LPS translocation through the compromised gastrointestinal tract during persistent HIV-1 infection and may serve as a potential target for immune intervention.
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产品类型：
产品号#：
19059
19059RF
17858
17858RF
100-0694
15025
15065
产品名：
EasySep™人单核细胞富集试剂盒
RoboSep™ 人单核细胞富集试剂盒含滤芯吸头
EasySep™人CD14正选试剂盒II
RoboSep™ 人CD14正选试剂盒II
EasySep™人CD14正选试剂盒II
RosetteSep™人NK细胞富集抗体混合物
RosetteSep™人NK细胞富集抗体混合物
Chalmers SA et al. (MAY 2016)
Scientific Reports 6 26164
Therapeutic Blockade of Immune Complex-Mediated Glomerulonephritis by Highly Selective Inhibition of Bruton's Tyrosine Kinase.
Lupus nephritis (LN) is a potentially dangerous end organ pathology that affects upwards of 60% of lupus patients. Bruton's tyrosine kinase (BTK) is important for B cell development,Fc receptor signaling,and macrophage polarization. In this study,we investigated the effects of a novel,highly selective and potent BTK inhibitor,BI-BTK-1,in an inducible model of LN in which mice receive nephrotoxic serum (NTS) containing anti-glomerular antibodies. Mice were treated once daily with vehicle alone or BI-BTK-1,either prophylactically or therapeutically. When compared with control treated mice,NTS-challenged mice treated prophylactically with BI-BTK-1 exhibited significantly attenuated kidney disease,which was dose dependent. BI-BTK-1 treatment resulted in decreased infiltrating IBA-1+ cells,as well as C3 deposition within the kidney. RT-PCR on whole kidney RNA and serum profiling indicated that BTK inhibition significantly decreased levels of LN-relevant inflammatory cytokines and chemokines. Renal RNA expression profiling by RNA-seq revealed that BI-BTK-1 dramatically modulated pathways related to inflammation and glomerular injury. Importantly,when administered therapeutically,BI-BTK-1 reversed established proteinuria and improved renal histopathology. Our results highlight the important role for BTK in the pathogenesis of immune complex-mediated nephritis,and BTK inhibition as a promising therapeutic target for LN.
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产品类型：
产品号#：
19359
19359RF
19054
19054RF
100-0697
产品名：
EasySep™人单核细胞分选试剂盒
RoboSep™ 人单核细胞分选试剂盒
EasySep™人B细胞富集试剂盒
RoboSep™ 人B细胞富集试剂盒含滤芯吸头
EasySep™人单核细胞分选试剂盒
Meierovics AI et al. (OCT 2016)
The Journal of experimental medicine
MAIT cells promote inflammatory monocyte differentiation into dendritic cells during pulmonary intracellular infection.
Mucosa-associated invariant T (MAIT) cells are a unique innate T cell subset that is necessary for rapid recruitment of activated CD4(+) T cells to the lungs after pulmonary F. tularensis LVS infection. Here,we investigated the mechanisms behind this effect. We provide evidence to show that MAIT cells promote early differentiation of CCR2-dependent monocytes into monocyte-derived DCs (Mo-DCs) in the lungs after F. tularensis LVS pulmonary infection. Adoptive transfer of Mo-DCs to MAIT cell-deficient mice (MR1(-/-) mice) rescued their defect in the recruitment of activated CD4(+) T cells to the lungs. We further demonstrate that MAIT cell-dependent GM-CSF production stimulated monocyte differentiation in vitro,and that in vivo production of GM-CSF was delayed in the lungs of MR1(-/-) mice. Finally,GM-CSF-deficient mice exhibited a defect in monocyte differentiation into Mo-DCs that was phenotypically similar to MR1(-/-) mice. Overall,our data demonstrate that MAIT cells promote early pulmonary GM-CSF production,which drives the differentiation of inflammatory monocytes into Mo-DCs. Further,this delayed differentiation of Mo-DCs in MR1(-/-) mice was responsible for the delayed recruitment of activated CD4(+) T cells to the lungs. These findings establish a novel mechanism by which MAIT cells function to promote both innate and adaptive immune responses.
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产品号#：
18970
18970RF
产品名：
EasySep™小鼠CD11b正选试剂盒II
RoboSep™ 小鼠CD11b正选试剂盒II
Akbar N et al. (SEP 2017)
JCI insight 2 17
Endothelium-derived extracellular vesicles promote splenic monocyte mobilization in myocardial infarction.
Transcriptionally activated monocytes are recruited to the heart after acute myocardial infarction (AMI). After AMI in mice and humans,the number of extracellular vesicles (EVs) increased acutely. In humans,EV number correlated closely with the extent of myocardial injury. We hypothesized that EVs mediate splenic monocyte mobilization and program transcription following AMI. Some plasma EVs bear endothelial cell (EC) integrins,and both proinflammatory stimulation of ECs and AMI significantly increased VCAM-1-positive EV release. Injected EC-EVs localized to the spleen and interacted with,and mobilized,splenic monocytes in otherwise naive,healthy animals. Analysis of human plasma EV-associated miRNA showed 12 markedly enriched miRNAs after AMI; functional enrichment analyses identified 1,869 putative mRNA targets,which regulate relevant cellular functions (e.g.,proliferation and cell movement). Furthermore,gene ontology termed positive chemotaxis as the most enriched pathway for the miRNA-mRNA targets. Among the identified EV miRNAs,EC-associated miRNA-126-3p and -5p were highly regulated after AMI. miRNA-126-3p and -5p regulate cell adhesion- and chemotaxis-associated genes,including the negative regulator of cell motility,plexin-B2. EC-EV exposure significantly downregulated plexin-B2 mRNA in monocytes and upregulated motility integrin ITGB2. These findings identify EVs as a possible novel signaling pathway by linking ischemic myocardium with monocyte mobilization and transcriptional activation following AMI.
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产品号#：
19861
19861RF
产品名：
EasySep™小鼠单核细胞分选试剂盒
RoboSep™ 小鼠单核细胞分选试剂盒
Capucha T et al. (JAN 2018)
The Journal of experimental medicine
Sequential BMP7/TGF-β1 signaling and microbiota instruct mucosal Langerhans cell differentiation.
Mucosal Langerhans cells (LCs) originate from pre-dendritic cells and monocytes. However,the mechanisms involved in their in situ development remain unclear. Here,we demonstrate that the differentiation of murine mucosal LCs is a two-step process. In the lamina propria,signaling via BMP7-ALK3 promotes translocation of LC precursors to the epithelium. Within the epithelium,TGF-β1 finalizes LC differentiation,and ALK5 is crucial to this process. Moreover,the local microbiota has a major impact on the development of mucosal LCs,whereas LCs in turn maintain mucosal homeostasis and prevent tissue destruction. These results reveal the differential and sequential role of TGF-β1 and BMP7 in LC differentiation and highlight the intimate interplay of LCs with the microbiota.
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产品类型：
产品号#：
19861
19861RF
19761
19761RF
产品名：
EasySep™小鼠单核细胞分选试剂盒
RoboSep™ 小鼠单核细胞分选试剂盒
X. Dong et al. (mar 2019)
Cellular molecular immunology
ACPAs promote IL-1beta production in rheumatoid arthritis by activating the NLRP3 inflammasome.
OBJECTIVES Anti-citrullinated protein antibodies (ACPAs) are a group of autoantibodies targeted against citrullinated proteins/peptides and are informative rheumatoid arthritis (RA) biomarkers. ACPAs also play a crucial role in RA pathogenesis,and their underlying mechanism merits investigation. METHODS Immunohistochemical (IHC) assays were carried out to determine IL-1beta levels in ACPA+ and ACPA- RA patients. PBMC-derived monocytes were differentiated into macrophages before stimulation with ACPAs purified from RA patients. The localization and interaction of molecules were analyzed by confocal microscopy,co-IP,and surface plasmon resonance. RESULTS In our study,we found that IL-1beta levels were elevated in ACPA+ RA patients and that ACPAs promoted IL-1beta production by PBMC-derived macrophages. ACPAs interacted with CD147 to enhance the interaction between CD147 and integrin beta1 and,in turn,activate the Akt/NF-kappaB signaling pathway. The nuclear localization of p65 promoted the expression of NLRP3 and pro-IL-1beta,resulting in priming. Moreover,ACPA stimulation activated pannexin channels,leading to ATP release. The accumulated ATP bound to the P2X7 receptor,leading to NLRP3 inflammasome activation. CONCLUSIONS Our study suggests a new hypothesis regarding IL-1beta production in RA involving ACPAs,which may be a potential therapeutic target in RA treatment.
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产品类型：
产品号#：
19058
19058RF
100-1525
产品名：
EasySep™人单核细胞富集试剂盒（不去除CD16）
RoboSep™ 人单核细胞富集试剂盒（不去除CD16）含滤芯吸头
EasySep™人单核细胞富集试剂盒（不去除CD16）
R. Lira-Junior et al. ( 2020)
Frontiers in immunology 11 86
S100A12 Expression Is Modulated During Monocyte Differentiation and Reflects Periodontitis Severity.
S100A12 is a calcium-binding protein of the S100 subfamily of myeloid-related proteins that acts as an alarmin to induce a pro-inflammatory innate immune response. It has been linked to several chronic inflammatory diseases,however its role in the common oral immunopathology periodontitis is largely unknown. Previous in vitro monoculture experiments indicate that S100A12 production decreases during monocyte differentiation stages,while the regulation within tissue is poorly defined. This study evaluated S100A12 expression in monocyte subsets,during monocyte-to-macrophage differentiation and following polarization,both in monoculture and in a tissue context,utilizing a three-dimensional co-culture oral tissue model. Further,we explored the involvement of S100A12 in periodontitis by analyzing its expression in peripheral circulation and gingival tissue,as well as in saliva. We found that S100A12 expression was higher in classical than in non-classical monocytes. S100A12 expression and protein secretion declined significantly during monocyte-to-macrophage differentiation,while polarization of monocyte-derived macrophages had no effect on either. Peripheral monocytes from periodontitis patients had higher S100A12 expression than monocytes from controls,a difference particularly observed in the intermediate and non-classical monocyte subsets. Further,monocytes from periodontitis patients displayed an increased secretion of S100A12 compared with monocytes from controls. In oral tissue cultures,monocyte differentiation resulted in increased S100A12 secretion over time,which further increased after inflammatory stimuli. Likewise,S100A12 expression was higher in gingival tissue from periodontitis patients where monocyte-derived cells exhibited higher expression of S100A12 in comparison to non-periodontitis tissue. In line with our findings,patients with severe periodontitis had significantly higher levels of S100A12 in saliva compared to non-periodontitis patients,and the levels correlated to clinical periodontal parameters. Taken together,S100A12 is predominantly secreted by monocytes rather than by monocyte-derived cells. Moreover,S100A12 is increased in inflamed tissue cultures,potentially as a result of enhanced production by monocyte-derived cells. This study implicates the involvement of S100A12 in periodontitis pathogenesis,as evidenced by increased S100A12 expression in inflamed gingival tissue,which may be due to altered circulatory monocytes in periodontitis.
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产品类型：
产品号#：
19058
19058RF
100-1525
产品名：
EasySep™人单核细胞富集试剂盒（不去除CD16）
RoboSep™ 人单核细胞富集试剂盒（不去除CD16）含滤芯吸头
EasySep™人单核细胞富集试剂盒（不去除CD16）
M. Syedbasha et al. (oct 2020)
Cell reports 33 1 108211
Interferon-$\lambda$ Enhances the Differentiation of Naive B Cells into Plasmablasts via the mTORC1 Pathway.
Type III interferon (interferon lambda [IFN-$\lambda$]) is known to be a potential immune modulator,but the mechanisms behind its immune-modulatory functions and its impact on plasmablast differentiation in humans remain unknown. Human B cells and their subtypes directly respond to IFN-$\lambda$. Using B cell transcriptome profiling,we investigate the immune-modulatory role of IFN-$\lambda$ in B cells. We find that IFN-$\lambda$-induced gene expression in B cells is steady,prolonged,and importantly,cell type specific. Furthermore,IFN-$\lambda$ enhances the mTORC1 (mammalian/mechanistic target of rapamycin complex 1) pathway in B cells activated by the B cell receptor (BCR/anti-IgM). Engagement of mTORC1 by BCR and IFN-$\lambda$ induces cell-cycle progress in B cells. Subsequently,IFN-$\lambda$ boosts the differentiation of naive B cells into plasmablasts upon activation,and the cells gain effector functions such as cytokine release (IL-6 and IL-10) and antibody production. Our study shows how IFN-$\lambda$ systematically boosts the differentiation of naive B cells into plasmablasts by enhancing the mTORC1 pathway and cell-cycle progression in activated B cells.
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EasySep™小鼠TIL（CD45）正选试剂盒
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