Marzaioli V et al. ( 2017)
Blood 130 15 1734--1745
NOX5 and p22phox are 2 novel regulators of human monocytic differentiation into dendritic cells.
Dendritic cells (DCs) are a heterogeneous population of professional antigen-presenting cells and are key cells of the immune system,acquiring different phenotypes in accordance with their localization during the immune response. A subset of inflammatory DCs is derived from circulating monocytes (Mo) and has a key role in inflammation and infection. The pathways controlling Mo-DC differentiation are not fully understood. Our objective was to investigate the possible role of nicotinamide adenine dinucleotide phosphate reduced form oxidases (NOXs) in Mo-DC differentiation. In this study,we revealed that Mo-DC differentiation was inhibited by NOX inhibitors and reactive oxygen species scavengers. We show that the Mo-DC differentiation was dependent on p22phox,and not on gp91phox/NOX2,as shown by the reduced Mo-DC differentiation observed in chronic granulomatous disease patients lacking p22phox. Moreover,we revealed that NOX5 expression was strongly increased during Mo-DC differentiation,but not during Mo-macrophage differentiation. NOX5 was expressed in circulating myeloid DC,and at a lower level in plasmacytoid DC. Interestingly,NOX5 was localized at the outer membrane of the mitochondria and interacted with p22phox in Mo-DC. Selective inhibitors and small interfering RNAs for NOX5 indicated that NOX5 controlled Mo-DC differentiation by regulating the JAK/STAT/MAPK and NFκB pathways. These data demonstrate that the NOX5-p22phox complex drives Mo-DC differentiation,and thus could be critical for immunity and inflammation.
View Publication
产品号#：
19061
19061RF
19062
19062RF
19359
19359RF
100-0697
产品名：
EasySep™人髓样DC富集试剂盒
RoboSep™ 人髓样DC富集试剂盒
EasySep™人浆细胞样DC富集试剂盒
RoboSep™ 人浆细胞样DC富集试剂盒含滤芯吸头
EasySep™人单核细胞分选试剂盒
RoboSep™ 人单核细胞分选试剂盒
EasySep™人单核细胞分选试剂盒
Wu X et al. (JAN 2018)
Cell 172 3 423--438.e25
Intrinsic Immunity Shapes Viral Resistance of Stem Cells.
Stem cells are highly resistant to viral infection compared to their differentiated progeny; however,the mechanism is mysterious. Here,we analyzed gene expression in mammalian stem cells and cells at various stages of differentiation. We find that,conserved across species,stem cells express a subset of genes previously classified as interferon (IFN) stimulated genes (ISGs) but that expression is intrinsic,as stem cells are refractory to interferon. This intrinsic ISG expression varies in a cell-type-specific manner,and many ISGs decrease upon differentiation,at which time cells become IFN responsive,allowing induction of a broad spectrum of ISGs by IFN signaling. Importantly,we show that intrinsically expressed ISGs protect stem cells against viral infection. We demonstrate the in vivo importance of intrinsic ISG expression for protecting stem cells and their differentiation potential during viral infection. These findings have intriguing implications for understanding stem cell biology and the evolution of pathogen resistance.
View Publication
产品号#：
02691
04434
04444
05110
05711
05712
05872
05873
18056
18056RF
72052
72054
72302
72304
72307
72308
70039
70039.1
70039.2
70039.3
70039.4
70039.5
70039.6
60062
60062BT
60062FI
60062FI.1
60062PE
60062PE.1
60045
60045AZ
60045AZ.1
60045BT
60045FI
60045FI.1
600
产品名：
StemSpan™ CD34+扩增添加物 (10X)
MethoCult™ H4434 Classic
MethoCult™ H4434 Classic
STEMdiff™定型内胚层检测试剂盒
NeuroCult™ SM1 神经添加物
CHIR99021
CHIR99021
Y-27632（二盐酸盐）
Y-27632（二盐酸盐）
Y-27632（二盐酸盐）
Y-27632（二盐酸盐）
抗人SSEA-4抗体，克隆号MC-813-70，生物素
抗人SSEA-4抗体，克隆号MC-813-70，FITC
抗人SSEA-4抗体, 克隆号MC-813-70，FITC
抗人SSEA-4抗体，克隆号MC-813-70，PE
抗人SSEA-4抗体，克隆号MC-813-70，PE
抗人CD90抗体，克隆5E10
抗人CD90抗体，克隆5E10，APC
抗人CD90抗体，克隆5E10，APC
抗人CD90抗体，克隆5E10，Biotin
抗人CD90抗体，克隆5E10，FITC
抗人CD90抗体，克隆5E10，FITC
Fan Y et al. (JAN 2018)
The Biochemical journal 475 1 23--44
Interrogating Parkinson's disease LRRK2 kinase pathway activity by assessing Rab10 phosphorylation in human neutrophils.
There is compelling evidence for the role of the leucine-rich repeat kinase 2 (LRRK2) and in particular its kinase function in Parkinson's disease. Orally bioavailable,brain penetrant and potent LRRK2 kinase inhibitors are in the later stages of clinical development. Here,we describe a facile and robust assay to quantify LRRK2 kinase pathway activity by measuring LRRK2-mediated phosphorylation of Rab10 in human peripheral blood neutrophils. We use the selective MJFF-pRab10 monoclonal antibody recognising the Rab10 Thr73 phospho-epitope that is phosphorylated by LRRK2. We highlight the feasibility and practicability of using our assay in the clinical setting by studying a few patients with G2019S LRRK2 associated and sporadic Parkinson's as well as healthy controls. We suggest that peripheral blood neutrophils are a valuable resource for LRRK2 research and should be considered for inclusion in Parkinson's bio-repository collections as they are abundant,homogenous and express relatively high levels of LRRK2 as well as Rab10. In contrast,the widely used peripheral blood mononuclear cells are heterogeneous and only a minority of cells (monocytes and contaminating neutrophils) express LRRK2. While our LRRK2 kinase pathway assay could assist in patient stratification based on LRRK2 kinase activity,we envision that it may find greater utility in pharmacodynamic and target engagement studies in future LRRK2 inhibitor trials.
View Publication
产品号#：
19666
85450
85460
100-0404
产品名：
EasySep™ Direct人中性粒细胞分选试剂盒
SepMate™-50 (IVD)
SepMate™-50 (IVD)
RoboSep™ 人中性粒细胞分选试剂盒
C. Yacoob et al. (JUN 2018)
PLoS pathogens 14 6 e1007120
B cell clonal lineage alterations upon recombinant HIV-1 envelope immunization of rhesus macaques.
Broadly neutralizing HIV-1 antibodies (bNAbs) isolated from infected subjects display protective potential in animal models. Their elicitation by immunization is thus highly desirable. The HIV-1 envelope glycoprotein (Env) is the sole viral target of bnAbs,but is also targeted by binding,non-neutralizing antibodies. Env-based immunogens tested so far in various animal species and humans have elicited binding and autologous neutralizing antibodies but not bNAbs (with a few notable exceptions). The underlying reasons for this are not well understood despite intensive efforts to characterize the binding specificities of the elicited antibodies; mostly by employing serologic methodologies and monoclonal antibody isolation and characterization. These approaches provide limited information on the ontogenies and clonal B cell lineages that expand following Env-immunization. Thus,our current understanding on how the expansion of particular B cell lineages by Env may be linked to the development of non-neutralizing antibodies is limited. Here,in addition to serological analysis,we employed high-throughput BCR sequence analysis from the periphery,lymph nodes and bone marrow,as well as B cell- and antibody-isolation and characterization methods,to compare in great detail the B cell and antibody responses elicited in non-human primates by two forms of the clade C HIV Env 426c: one representing the full length extracellular portion of Env while the other lacking the variable domains 1,2 and 3 and three conserved N-linked glycosylation sites. The two forms were equally immunogenic,but only the latter elicited neutralizing antibodies by stimulating a more restricted expansion of B cells to a narrower set of IGH/IGK/IGL-V genes that represented a small fraction (0.003-0.02{\%}) of total B cells. Our study provides new information on how Env antigenic differences drastically affect the expansion of particular B cell lineages and supports immunogen-design efforts aiming at stimulating the expansion of cells expressing particular B cell receptors.
View Publication
产品号#：
85415
85420
85450
85460
86415
86420
86450
86460
产品名：
SepMate™-15 (IVD)
SepMate™-15 (IVD)
SepMate™-50 (IVD)
SepMate™-50 (IVD)
SepMate™-15 (RUO)
SepMate™-15 (RUO)
SepMate™-50 (RUO)
SepMate™-50 (RUO)
Chen WLK et al. ( 2017)
Biotechnology and bioengineering 114 11 2648--2659
Integrated gut/liver microphysiological systems elucidates inflammatory inter-tissue crosstalk.
A capability for analyzing complex cellular communication among tissues is important in drug discovery and development,and in vitro technologies for doing so are required for human applications. A prominent instance is communication between the gut and the liver,whereby perturbations of one tissue can influence behavior of the other. Here,we present a study on human gut-liver tissue interactions under normal and inflammatory contexts,via an integrative multi-organ platform comprising human liver (hepatocytes and Kupffer cells),and intestinal (enterocytes,goblet cells,and dendritic cells) models. Our results demonstrated long-term (>2 weeks) maintenance of intestinal (e.g.,barrier integrity) and hepatic (e.g.,albumin) functions in baseline interaction. Gene expression data comparing liver in interaction with gut,versus isolation,revealed modulation of bile acid metabolism. Intestinal FGF19 secretion and associated inhibition of hepatic CYP7A1 expression provided evidence of physiologically relevant gut-liver crosstalk. Moreover,significant non-linear modulation of cytokine responses was observed under inflammatory gut-liver interaction; for example,production of CXCR3 ligands (CXCL9,10,11) was synergistically enhanced. RNA-seq analysis revealed significant upregulation of IFNα/β/γ signaling during inflammatory gut-liver crosstalk,with these pathways implicated in the synergistic CXCR3 chemokine production. Exacerbated inflammatory response in gut-liver interaction also negatively affected tissue-specific functions (e.g.,liver metabolism). These findings illustrate how an integrated multi-tissue platform can generate insights useful for understanding complex pathophysiological processes such as inflammatory organ crosstalk. Biotechnol. Bioeng. 2017;114: 2648-2659. textcopyright 2017 Wiley Periodicals,Inc.
View Publication
产品号#：
19058
19058RF
70500
70500.1
70500.2
200-0092
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）
Chang C-F et al. (DEC 2017)
The Journal of clinical investigation
Erythrocyte efferocytosis modulates macrophages towards recovery after intracerebral hemorrhage.
Macrophages are a source of both proinflammatory and restorative functions in damaged tissue through complex dynamic phenotypic changes. Here,we sought to determine whether monocyte-derived macrophages (MDMs) contribute to recovery after acute sterile brain injury. By profiling the transcriptional dynamics of MDMs in the murine brain after experimental intracerebral hemorrhage (ICH),we found robust phenotypic changes in the infiltrating MDMs over time and demonstrated that MDMs are essential for optimal hematoma clearance and neurological recovery. Next,we identified the mechanism by which the engulfment of erythrocytes with exposed phosphatidylserine directly modulated the phenotype of both murine and human MDMs. In mice,loss of receptor tyrosine kinases AXL and MERTK reduced efferocytosis of eryptotic erythrocytes and hematoma clearance,worsened neurological recovery,exacerbated iron deposition,and decreased alternative activation of macrophages after ICH. Patients with higher circulating soluble AXL had poor 1-year outcomes after ICH onset,suggesting that therapeutically augmenting efferocytosis may improve functional outcomes by both reducing tissue injury and promoting the development of reparative macrophage responses. Thus,our results identify the efferocytosis of eryptotic erythrocytes through AXL/MERTK as a critical mechanism modulating macrophage phenotype and contributing to recovery from ICH.
View Publication
产品号#：
17858
17858RF
85450
85460
100-0694
产品名：
EasySep™人CD14正选试剂盒II
RoboSep™ 人CD14正选试剂盒II
SepMate™-50 (IVD)
SepMate™-50 (IVD)
EasySep™人CD14正选试剂盒II
Zhang Y et al. ( 2018)
Nature communications 9 1 6
Nanoparticle anchoring targets immune agonists to tumors enabling anti-cancer immunity without systemic toxicity.
Immunostimulatory agents such as agonistic anti-CD137 and interleukin (IL)-2 generate effective anti-tumor immunity but also elicit serious toxicities,hampering their clinical application. Here we show that combination therapy with anti-CD137 and an IL-2-Fc fusion achieves significant initial anti-tumor activity,but also lethal immunotoxicity deriving from stimulation of circulating leukocytes. To overcome this toxicity,we demonstrate that anchoring IL-2 and anti-CD137 on the surface of liposomes allows these immune agonists to rapidly accumulate in tumors while lowering systemic exposure. In multiple tumor models,immunoliposome delivery achieves anti-tumor activity equivalent to free IL-2/anti-CD137 but with the complete absence of systemic toxicity. Immunoliposomes stimulated tumor infiltration by cytotoxic lymphocytes,cytokine production,and granzyme expression,demonstrating equivalent immunostimulatory effects to the free drugs in the local tumor microenvironment. Thus,surface-anchored particle delivery may provide a general approach to exploit the potent stimulatory activity of immune agonists without debilitating systemic toxicities.
View Publication
产品号#：
19753
19753RF
产品名：
Xu MM et al. (AUG 2017)
Immunity 47 2 363--373.e5
Dendritic Cells but Not Macrophages Sense Tumor Mitochondrial DNA for Cross-priming through Signal Regulatory Protein α Signaling.
Inhibition of cytosolic DNA sensing represents a strategy that tumor cells use for immune evasion,but the underlying mechanisms are unclear. Here we have shown that CD47-signal regulatory protein α (SIRPα) axis dictates the fate of ingested DNA in DCs for immune evasion. Although macrophages were more potent in uptaking tumor DNA,increase of DNA sensing by blocking the interaction of SIRPα with CD47 preferentially occurred in dendritic cells (DCs) but not in macrophages. Mechanistically,CD47 blockade enabled the activation of NADPH oxidase NOX2 in DCs,which in turn inhibited phagosomal acidification and reduced the degradation of tumor mitochondrial DNA (mtDNA) in DCs. mtDNA was recognized by cyclic-GMP-AMP synthase (cGAS) in the DC cytosol,contributing to type I interferon (IFN) production and antitumor adaptive immunity. Thus,our findings have demonstrated how tumor cells inhibit innate sensing in DCs and suggested that the CD47-SIRPα axis is critical for DC-driven antitumor immunity.
View Publication
产品号#：
18780
18780RF
18781
18781RF
19853
19853RF
70025
70025.1
70025.2
70025.3
产品名：
EasySep™小鼠CD11c正选试剂盒II
RoboSep™ 小鼠CD11c正选试剂盒II
EasySep™小鼠CD11c正选试剂盒II及脾脏解离液
RoboSep™ 小鼠CD11c正选试剂盒II及脾脏解离液
EasySep™小鼠CD8+ T细胞分选试剂盒
RoboSep™ 小鼠CD8+ T细胞分选试剂盒
冻存的人外周血单个核细胞
冻存的人外周血单个核细胞
冻存的人外周血单个核细胞
冻存的人外周血单个核细胞
C.-W. J. Lio et al. (apr 2019)
Science immunology 4 34
TET enzymes augment activation-induced deaminase (AID) expression via 5-hydroxymethylcytosine modifications at the Aicda superenhancer.
TET enzymes are dioxygenases that promote DNA demethylation by oxidizing the methyl group of 5-methylcytosine to 5-hydroxymethylcytosine (5hmC). Here,we report a close correspondence between 5hmC-marked regions,chromatin accessibility and enhancer activity in B cells,and a strong enrichment for consensus binding motifs for basic region-leucine zipper (bZIP) transcription factors at TET-responsive genomic regions. Functionally,Tet2 and Tet3 regulate class switch recombination (CSR) in murine B cells by enhancing expression of Aicda,which encodes the activation-induced cytidine deaminase (AID) enzyme essential for CSR. TET enzymes deposit 5hmC,facilitate DNA demethylation,and maintain chromatin accessibility at two TET-responsive enhancer elements,TetE1 and TetE2,located within a superenhancer in the Aicda locus. Our data identify the bZIP transcription factor,ATF-like (BATF) as a key transcription factor involved in TET-dependent Aicda expression. 5hmC is not deposited at TetE1 in activated Batf-deficient B cells,indicating that BATF facilitates TET recruitment to this Aicda enhancer. Our study emphasizes the importance of TET enzymes for bolstering AID expression and highlights 5hmC as an epigenetic mark that captures enhancer dynamics during cell activation.
View Publication
产品号#：
19854
19854RF
产品名：
EasySep™小鼠B细胞分选试剂盒
RoboSep™ 小鼠B细胞分选试剂盒
Pekalski ML et al. (AUG 2017)
JCI insight 2 16
Neonatal and adult recent thymic emigrants produce IL-8 and express complement receptors CR1 and CR2.
The maintenance of peripheral naive T lymphocytes in humans is dependent on their homeostatic division,not continuing emigration from the thymus,which undergoes involution with age. However,postthymic maintenance of naive T cells is still poorly understood. Previously we reported that recent thymic emigrants (RTEs) are contained in CD31+CD25- naive T cells as defined by their levels of signal joint T cell receptor rearrangement excision circles (sjTRECs). Here,by differential gene expression analysis followed by protein expression and functional studies,we define that the naive T cells having divided the least since thymic emigration express complement receptors (CR1 and CR2) known to bind complement C3b- and C3d-decorated microbial products and,following activation,produce IL-8 (CXCL8),a major chemoattractant for neutrophils in bacterial defense. We also observed an IL-8-producing memory T cell subpopulation coexpressing CR1 and CR2 and with a gene expression signature resembling that of RTEs. The functions of CR1 and CR2 on T cells remain to be determined,but we note that CR2 is the receptor for Epstein-Barr virus,which is a cause of T cell lymphomas and a candidate environmental factor in autoimmune disease.
View Publication
产品号#：
15022
15062
产品名：
RosetteSep™人CD4+ T细胞富集抗体混合物
RosetteSep™人CD4+ T细胞富集抗体混合物
Tan Q et al. (JAN 2018)
JCI insight 3 1
Activation-induced cytidine deaminase deficiency accelerates autoimmune diabetes in NOD mice.
B cells play an important role in type 1 diabetes (T1D) development. However,the role of B cell activation-induced cytidine deaminase (AID) in diabetes development is not clear. We hypothesized that AID is important in the immunopathogenesis of T1D. To test this hypothesis,we generated AID-deficient (AID-/-) NOD mice. We found that AID-/-NOD mice developed accelerated T1D,with worse insulitis and high levels of anti-insulin autoantibody in the circulation. Interestingly,neither maternal IgG transferred through placenta,nor IgA transferred through milk affected the accelerated diabetes development. AID-/-NOD mice showed increased activation and proliferation of B and T cells. We found enhanced T-B cell interactions in AID-/-NOD mice,with increased T-bet and IFN-γ expression in CD4+ T cells in the presence of AID-/- B cells. Moreover,excessive lymphoid expansion was observed in AID-/-NOD mice. Importantly,antigen-specific BDC2.5 CD4+ T cells caused more rapid onset of diabetes when cotransferred with AID-/- B cells than when cotransferred with AID+/+ B cells. Thus,our study provides insights into the role of AID in T1D. Our data also suggest that AID is a negative regulator of immune tolerance and ablation of AID can lead to exacerbated islet autoimmunity and accelerated T1D development.
View Publication
产品号#：
19854
19854RF
产品名：
EasySep™小鼠B细胞分选试剂盒
RoboSep™ 小鼠B细胞分选试剂盒
Hideshima T et al. (FEB 2003)
Blood 101 4 1530--4
Molecular mechanisms mediating antimyeloma activity of proteasome inhibitor PS-341.
We have recently shown that proteasome inhibitor PS-341 induces apoptosis in drug-resistant multiple myeloma (MM) cells,inhibits binding of MM cells in the bone marrow microenvironment,and inhibits cytokines mediating MM cell growth,survival,drug resistance,and migration in vitro. PS-341 also inhibits human MM cell growth and prolongs survival in a SCID mouse model. Importantly,PS-341 has achieved remarkable clinical responses in patients with refractory relapsed MM. We here demonstrate molecular mechanisms whereby PS-341 mediates anti-MM activity by inducing p53 and MDM2 protein expression; inducing the phosphorylation (Ser15) of p53 protein; activating c-Jun NH(2)-terminal kinase (JNK),caspase-8,and caspase-3; and cleaving the DNA protein kinase catalytic subunit,ATM,and MDM2. Inhibition of JNK activity abrogates PS-341-induced MM cell death. These studies identify molecular targets of PS-341 and provide the rationale for the development of second-generation,more targeted therapies.
View Publication
EasySep™小鼠TIL（CD45）正选试剂盒
沪公网安备31010102008431号