B. Westerhuis et al. (feb 2020)
Scientific reports 10 1 3152
Specific memory B cell response in humans upon infection with highly pathogenic H7N7 avian influenza virus.
H7 avian influenza viruses represent a major public health concern,and worldwide outbreaks raise the risk of a potential pandemic. Understanding the memory B cell response to avian (H7) influenza virus infection in humans could provide insights in the potential key to human infection risks. We investigated an epizootic of the highly pathogenic A(H7N7) in the Netherlands,which in 2003 led to infection of 89 persons and one fatal case. Subtype-specificity of antibodies were determined for confirmed H7N7 infected individuals (cases) (n = 19),contacts of these cases (n = 21) and a comparison group controls (n = 16),by microarray,using recombinant hemagglutinin (HA)1 proteins. The frequency and specificity of memory B cells was determined by detecting subtype-specific antibodies in the culture supernatants from in vitro stimulated oligoclonal B cell cultures,from peripheral blood of cases and controls. All cases (100{\%}) had high antibody titers specific for A(H7N7)2003 (GMT {\textgreater} 100),whereas H7-HA1 antigen binding was detected in 29{\%} of contacts and 31{\%} of controls,suggesting that some of the H7 reactivity stems from cross reactive antibodies. To unravel homotypic and heterotypic responses,the frequency and specificity of memory B cells were determined in 2 cases. Ten of 123 HA1 reactive clones isolated from the cases bound to only H7- HA1,whereas 5 bound both H7 and other HA1 antigens. We recovered at least four different epitopal reactivities,though none of the H7 reactive antibodies were able to neutralize H7 infections in vitro. Our study serologically confirms the infection with H7 avian influenza viruses,and shows that H7 infection triggers a mixture of strain -specific and cross-reactive antibodies.
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产品类型：
产品号#：
17854
17854RF
产品名：
EasySep™人CD19正选试剂盒II
RoboSep™ 人CD19正选试剂盒II
H. Xie et al. (jan 2020)
Scientific reports 10 1 766
Silencing of SENP2 in Multiple Myeloma Induces Bortezomib Resistance by Activating NF-$\kappa$B Through the Modulation of I$\kappa$B$\alpha$ Sumoylation.
The proteasome inhibitor bortezomib is the most successfully applied chemotherapeutic drug for treating multiple myeloma. However,its clinical efficacy reduced due to resistance development. The underlying molecular mechanisms of bortezomib resistance are poorly understood. In this study,by combining in silico analysis and sgRNA library based drug resistance screening assay,we identified SENP2 (Sentrin/SUMO-specific proteases-2) as a bortezomib sensitive gene and found its expression highly downregulated in bortezomib resistant multiple myeloma patient's samples. Furthermore,down regulation of SENP2 in multiple myeloma cell line RPMI8226 alleviated bortezomib induced cell proliferation inhibition and apoptosis,whereas,overexpression of SENP2 sensitized these cells to bortezomib treatment. We further demonstrate that knockdown of SENP2 in RPMI8226 cells increased SUMO2 conjugated I$\kappa$B$\alpha$ that resulted in the activation of NF-$\kappa$B. Taken together,we report that silencing of SENP2 and consequent activation of NF-$\kappa$B through the modulation of I$\kappa$B$\alpha$ sumoylation as a novel mechanism inducing bortezomib resistance in multiple myeloma.
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产品类型：
产品号#：
17877
17877RF
产品名：
EasySep™人CD138正选试剂盒 II
RoboSep™ 人CD138正选试剂盒 II
F. Beguier et al. (aug 2020)
Immunity 53 2 429--441.e8
The 10q26 Risk Haplotype of Age-Related Macular Degeneration Aggravates Subretinal Inflammation by Impairing Monocyte Elimination.
A minor haplotype of the 10q26 locus conveys the strongest genetic risk for age-related macular degeneration (AMD). Here,we examined the mechanisms underlying this susceptibility. We found that monocytes from homozygous carriers of the 10q26 AMD-risk haplotype expressed high amounts of the serine peptidase HTRA1,and HTRA1 located to mononuclear phagocytes (MPs) in eyes of non-carriers with AMD. HTRA1 induced the persistence of monocytes in the subretinal space and exacerbated pathogenic inflammation by hydrolyzing thrombospondin 1 (TSP1),which separated the two CD47-binding sites within TSP1 that are necessary for efficient CD47 activation. This HTRA1-induced inhibition of CD47 signaling induced the expression of pro-inflammatory osteopontin (OPN). OPN expression increased in early monocyte-derived macrophages in 10q26 risk carriers. In models of subretinal inflammation and AMD,OPN deletion or pharmacological inhibition reversed HTRA1-induced pathogenic MP persistence. Our findings argue for the therapeutic potential of CD47 agonists and OPN inhibitors for the treatment of AMD.
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产品类型：
产品号#：
19059
19861
19861RF
19059RF
产品名：
EasySep™人单核细胞富集试剂盒
EasySep™小鼠单核细胞分选试剂盒
RoboSep™ 小鼠单核细胞分选试剂盒
RoboSep™ 人单核细胞富集试剂盒含滤芯吸头
B. V. Le et al. (oct 2020)
Cell reports 33 1 108221
TGF$\beta$R-SMAD3 Signaling Induces Resistance to PARP Inhibitors in the Bone Marrow Microenvironment.
Synthetic lethality triggered by PARP inhibitor (PARPi) yields promising therapeutic results. Unfortunately,tumor cells acquire PARPi resistance,which is usually associated with the restoration of homologous recombination,loss of PARP1 expression,and/or loss of DNA double-strand break (DSB) end resection regulation. Here,we identify a constitutive mechanism of resistance to PARPi. We report that the bone marrow microenvironment (BMM) facilitates DSB repair activity in leukemia cells to protect them against PARPi-mediated synthetic lethality. This effect depends on the hypoxia-induced overexpression of transforming growth factor beta receptor (TGF$\beta$R) kinase on malignant cells,which is activated by bone marrow stromal cells-derived transforming growth factor beta 1 (TGF-$\beta$1). Genetic and/or pharmacological targeting of the TGF-$\beta$1-TGF$\beta$R kinase axis results in the restoration of the sensitivity of malignant cells to PARPi in BMM and prolongs the survival of leukemia-bearing mice. Our finding may lead to the therapeutic application of the TGF$\beta$R inhibitor in patients receiving PARPis.
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产品类型：
产品号#：
18757
18757RF
产品名：
EasySep™小鼠CD117（cKIT）正选试剂盒
RoboSep™ 小鼠CD117（cKIT）正选试剂盒含滤芯吸头
I. L. Roth et al. (oct 2020)
Journal of clinical immunology 40 7 977--986
Chronic granulomatous disease (CGD) is a rare primary immunodeficiency disorder caused by defects in the NADPH oxidase complex. Mutations in NCF2 encoding the cytosolic factor p67phox result in autosomal recessive CGD. We describe three patients with a novel c.855G{\textgreater}C NCF2 mutation presenting with diverse clinical phenotype. Two siblings were heterozygous for the novel mutation and for a previously described exon 8-9 duplication,while a third unrelated patient was homozygous for the novel mutation. Mutation pathogenicity was confirmed by abnormal DHR123 assay and absent p67phox production and by sequencing of cDNA which showed abnormal RNA splicing. Clinically,the homozygous patient presented with suspected early onset interstitial lung disease and NCF2 mutation was found on genetic testing performed in search for surfactant-related defects. The two siblings also had variable presentation with one having history of severe pneumonia,lymphadenitis,and recurrent skin abscesses and the other presenting in his 30s with discoid lupus erythematosus and without significant infectious history. We therefore identified a novel pathogenic NCF2 mutation causing diverse and unusual clinical phenotype.
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产品类型：
产品号#：
17957
17957RF
产品名：
EasySep™人中性粒细胞分选试剂盒
RoboSep™ 人中性粒细胞分选试剂盒
W. Zheng et al. (oct 2020)
Cancer research
RIG-I-like receptor LGP2 is required for tumor control by radiation therapy.
Dendritic cells (DC) play an essential role in innate immunity and radiation-elicited immune responses. LGP2 is a RIG-I like receptor (RLR) involved in cytoplasmic RNA recognition and anti-viral responses. Although LGP2 has also been linked to cell survival of both tumor cells and T cells,the role of LGP2 in mediating DC function and anti-tumor immunity elicited by radiotherapy remains unclear. Here we report that tumor DC are linked to the clinical outcome of breast cancer patients who received radiotherapy (RT) and the presence of DC correlates with gene expression of LGP2 in the tumor microenvironment. In preclinical models,host LGP2 was essential for optimal anti-tumor control by ionizing radiation (IR). The absence of LGP2 in DC dampened type I interferon production and the priming capacity of DC. In the absence of LGP2,MDA5-mediated activation of type I IFN signaling was abrogated. The MDA5/LGP2 agonist high molecular weight poly I: C improved the anti-tumor effect of IR. This study reveals a previously undefined role of LGP2 in host immunity and provides a new strategy to improve the efficacy of radiotherapy.
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产品类型：
产品号#：
18953
18953RF
产品名：
EasySep™小鼠CD8a正选试剂盒II
RoboSep™ 小鼠CD8a正选试剂盒II
&Scaron et al. (JUL 2013)
Journal of immunology (Baltimore,Md. : 1950) 191 2 828--36
CD160 activation by herpesvirus entry mediator augments inflammatory cytokine production and cytolytic function by NK cells.
Lymphocyte activation is regulated by costimulatory and inhibitory receptors,of which both B and T lymphocyte attenuator (BTLA) and CD160 engage herpesvirus entry mediator (HVEM). Notably,it remains unclear how HVEM functions with each of its ligands during immune responses. In this study,we show that HVEM specifically activates CD160 on effector NK cells challenged with virus-infected cells. Human CD56(dim) NK cells were costimulated specifically by HVEM but not by other receptors that share the HVEM ligands LIGHT,Lymphotoxin-α,or BTLA. HVEM enhanced human NK cell activation by type I IFN and IL-2,resulting in increased IFN-γ and TNF-α secretion,and tumor cell-expressed HVEM activated CD160 in a human NK cell line,causing rapid hyperphosphorylation of serine kinases ERK1/2 and AKT and enhanced cytolysis of target cells. In contrast,HVEM activation of BTLA reduced cytolysis of target cells. Together,our results demonstrate that HVEM functions as a regulator of immune function that activates NK cells via CD160 and limits lymphocyte-induced inflammation via association with BTLA.
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产品类型：
产品号#：
19055
19055RF
产品名：
EasySep™人NK细胞富集试剂盒
RoboSep™ 人NK细胞富集试剂盒含滤芯吸头
Al-Jaderi Z and Maghazachi AA (NOV 2013)
Toxins 5 11 1932--47
Effects of vitamin D3, calcipotriol and FTY720 on the expression of surface molecules and cytolytic activities of human natural killer cells and dendritic cells.
We describe here the effects of three drugs that are either approved or have the potential for treating multiple sclerosis (MS) patients through the in vitro activities of human natural killer (NK) cells and dendritic cells (DCs). Our results indicate that 1,25(OH)2D3,the biologically active metabolite of vitamin D3,calcipotriol and FTY720 augment IL-2-activated NK cell lysis of K562 and RAJI tumor cell lines as well as immature (i) and mature (m) DCs,with variable efficacies. These results are corroborated with the ability of the drugs to up-regulate the expression of NK cytotoxicity receptors NKp30 and NKp44,as well as NKG2D on the surfaces of NK cells. Also,they down-regulate the expression of the killer inhibitory receptor CD158. The three drugs down-regulate the expression of CCR6 on the surface of iDCs,whereas vitamin D3 and calcipotriol tend to up-regulate the expression of CCR7 on mDCs,suggesting that they may influence the migration of DCs into the lymph nodes. Finally,vitamin D3,calcipotriol and FTY720 enhance NK17/NK1 cell lysis of K562 cells,suggesting that a possible mechanism of action for these drugs is via activating these newly described cells. In conclusion,our results show novel mechanisms of action for vitamin D3,calcipotriol and FTY720 on cells of the innate immune system.
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产品类型：
产品号#：
18055
18055RF
15025
15065
15028
15068
产品名：
RosetteSep™人NK细胞富集抗体混合物
RosetteSep™人NK细胞富集抗体混合物
RosetteSep™ 人单核细胞富集抗体混合物
RosetteSep™人单核细胞富集抗体混合物
Tang MLF et al. ( 2014)
The European Journal of Immunology 44 4 1108--1118
The DNA damage response induces antigen presenting cell-like functions in fibroblasts
The DNA damage response (DDR) alerts the immune system to the danger posed by DNA damage through the induction of damage-associated molecular pattern molecules,chemokines,and ligands for activating immune receptors such as lymphocyte function-associated antigen 1 (LFA-1),NKG2D,and DNAX accessory molecule 1 (DNAM-1). Here we provide evidence that OVA(257-264) -pulsed fibroblasts gain the ability to activate naïve OT-I CD8(+) T cells in response to DNA damage. The ability of fibroblasts to activate OT-I CD8(+) T cells depended on the upregulation of ICAM-1 on fibroblasts and DNAM-1 expression of CD8(+) T cells. OVA(257-264) -pulsed fibroblasts were able to induce a protective T-cell response against B16-OVA cells in a DDR-dependent manner. Hence,the DDR may alert the immune system to the presence of potentially dangerous cells by upregulating the expression of ligands that can induce the activation of innate and adaptive immune cells.
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产品类型：
产品号#：
19853
19853RF
产品名：
EasySep™小鼠CD8+ T细胞分选试剂盒
RoboSep™ 小鼠CD8+ T细胞分选试剂盒
Voo KS et al. (JUL 2014)
The Journal of Immunology 193 2 627--34
Targeting of TLRs inhibits CD4+ regulatory T cell function and activates lymphocytes in human peripheral blood mononuclear cells.
Accumulating evidence suggests elements within tumors induce exhaustion of effector T cells and infiltration of immunosuppressive regulatory T cells (Tregs),thus preventing the development of durable antitumor immunity. Therefore,the discovery of agents that simultaneously block Treg suppressive function and reinvigorate effector function of lymphocytes is key to the development of effective cancer immunotherapy. Previous studies have shown that TLR ligands (TLRLs) could modulate the function of these T cell targets; however,those studies relied on cell-free or accessory cell-based assay systems that do not accurately reflect in vivo responses. In contrast,we used a human PBMC-based proliferation assay system to simultaneously monitor the effect of TLRLs on T cells (CD4(+),CD8(+),Tregs),B cells,and NK cells,which gave different and even conflicting results. We found that the TLR7/8L:CL097 could simultaneously activate CD8(+) T cells,B cells,and NK cells plus block Treg suppression of T cells and B cells. The TLRLs TLR1/2L:Pam3CSK4,TLR5L:flagellin,TLR4L:LPS,and TLR8/7L:CL075 also blocked Treg suppression of CD4(+) or CD8(+) T cell proliferation,but not B cell proliferation. Besides CL097,TLR2L:PGN,CL075,and TLR9L:CpG-A,CpG-B,and CpG-C) were strong activators of NK cells. Importantly,we found that Pam3CSK4 could: 1) activate CD4(+) T cell proliferation,2) inhibit the expansion of IL-10(+) naturally occurring FOXP3(+) Tregs and induction of IL-10(+) CD4(+) Tregs (IL-10-producing type 1 Treg),and 3) block naturally occurring FOXP3(+) Tregs suppressive function. Our results suggest these agents could serve as adjuvants to enhance the efficacy of current immunotherapeutic strategies in cancer patients.
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产品类型：
产品号#：
19052
19052RF
19055
19055RF
产品名：
EasySep™人CD4+ T细胞富集试剂盒
RoboSep™ 人CD4+ T细胞富集试剂盒含滤芯吸头
EasySep™人NK细胞富集试剂盒
RoboSep™ 人NK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
Song W et al. (OCT 2016)
Journal of Biomedical Materials Research - Part A 104 3 678--687
Efficient generation of endothelial cells from human pluripotent stem cells and characterization of their functional properties
Although endothelial cells (ECs) have been derived from human pluripotent stem cells (hPSCs),large-scale generation of hPSC-ECs remains challenging and their functions are not well characterized. Here we report a simple and efficient three-stage method that allows generation of approximately 98 and 9500 ECs on day 16 and day 34,respectively,from each human embryonic stem cell (hESC) input. The functional properties of hESC-ECs derived in the presence and absence of a TGF$$-inhibitory molecule SB431542 were characterized and compared with those of human umbilical vein endothelial cells (HUVECs). Confluent monolayers formed by SB431542(+) hESC-ECs,SB431542(-) hESC-ECs,and HUVECs showed similar permeability to 10,000 Da dextran,but these cells exhibited striking differences in forming tube-like structures in 3D fibrin gels. The SB431542(+) hESC-ECs were most potent in forming tube-like structures regardless of whether VEGF and bFGF were present in the medium; less potent SB431542(-) hESC-ECs and HUVECs responded differently to VEGF and bFGF,which significantly enhanced the ability of HUVECs to form tube-like structures but had little impact on SB431542(-) hESC-ECs. This study offers an efficient approach to large-scale hPSC-EC production and suggests that the phenotypes and functions of hPSC-ECs derived under different conditions need to be thoroughly examined before their use in technology development. This article is protected by copyright. All rights reserved.
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EasySep™小鼠TIL（CD45）正选试剂盒
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