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.
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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
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.
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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
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.
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产品号#：
19753
19753RF
产品名：
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.
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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
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.
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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）
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.
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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
Freeman SA et al. (JAN 2018)
Cell 172 2-Jan 305--317.e10
Transmembrane Pickets Connect Cyto- and Pericellular Skeletons Forming Barriers to Receptor Engagement.
Phagocytic receptors must diffuse laterally to become activated upon clustering by multivalent targets. Receptor diffusion,however,can be obstructed by transmembrane proteins (pickets") that are immobilized by interacting with the cortical cytoskeleton. The molecular identity of these pickets and their role in phagocytosis have not been defined. We used single-molecule tracking to study the interaction between Fcγ receptors and CD44 an abundant transmembrane protein capable of indirect association with F-actin hence likely to serve as a picket. CD44 tethers reversibly to formin-induced actin filaments curtailing receptor diffusion. Such linear filaments predominate in the trailing end of polarized macrophages where receptor mobility was minimal. Conversely receptors were most mobile at the leading edge where Arp2/3-driven actin branching predominates. CD44 binds hyaluronan anchoring a pericellular coat that also limits receptor displacement and obstructs access to phagocytic targets. Force must be applied to traverse the pericellular barrier enabling receptors to engage their targets.
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产品号#：
19359
19359RF
60068
60068.1
60068AD
60068AD.1
60068AZ
60068AZ.1
60068BT
60068BT.1
60068FI
60068FI.1
60068PE
60068PE.1
60068PS
60068PS.1
60012
60012FI
60012FI.1
100-0697
100-1574
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
抗小鼠CD44抗体，克隆IM7
抗小鼠CD44抗体，克隆IM7
抗小鼠CD44抗体，clone IM7，Alexa Fluor® 488
抗小鼠CD44抗体，克隆IM7，Alexa Fluor® 488
抗小鼠CD44抗体，克隆IM7，APC
抗小鼠CD44抗体，克隆IM7，APC
抗小鼠CD44抗体，克隆IM7，Biotin
抗小鼠CD44抗体，克隆IM7，Biotin
抗小鼠CD44抗体，克隆IM7，FITC
抗小鼠CD44抗体，克隆IM7，PE
抗小鼠CD44抗体，克隆IM7，PE
抗小鼠CD44抗体，克隆IM7，PerCP-Cy5.5
抗人CD32抗体，克隆IV.3
抗人CD32抗体，clone IV.3，FITC
EasySep™人单核细胞分选试剂盒
抗人CD32抗体，克隆IV.3，FITC
He W et al. (NOV 2017)
Cancer research 77 22 6375--6388
CD155T/TIGIT Signaling Regulates CD8+ T-cell Metabolism and Promotes Tumor Progression in Human Gastric Cancer.
The T-cell surface molecule TIGIT is an immune checkpoint molecule that inhibits T-cell responses,but its roles in cancer are little understood. In this study,we evaluated the role TIGIT checkpoint plays in the development and progression of gastric cancer. We show that the percentage of CD8 T cells that are TIGIT+ was increased in gastric cancer patients compared with healthy individuals. These cells showed functional exhaustion with impaired activation,proliferation,cytokine production,and metabolism,all of which were rescued by glucose. In addition,gastric cancer tissue and cell lines expressed CD155,which bound TIGIT receptors and inactivated CD8 T cells. In a T cell-gastric cancer cell coculture system,gastric cancer cells deprived CD8 T cells of glucose and impaired CD8 T-cell effector functions; these effects were neutralized by the additional glucose or by TIGIT blockade. In gastric cancer tumor cells,CD155 silencing increased T-cell metabolism and IFNγ production,whereas CD155 overexpression inhibited T-cell metabolism and IFNγ production; this inhibition was neutralized by TIGIT blockade. Targeting CD155/TIGIT enhanced CD8 T-cell reaction and improved survival in tumor-bearing mice. Combined targeting of TIGIT and PD-1 further enhanced CD8 T-cell activation and improved survival in tumor-bearing mice. Our results suggest that gastric cancer cells inhibit CD8 T-cell metabolism through CD155/TIGIT signaling,which inhibits CD8 T-cell effector functions,resulting in hyporesponsive antitumor immunity. These findings support the candidacy of CD155/TIGIT as a potential therapeutic target in gastric cancer. Cancer Res; 77(22); 6375-88. textcopyright2017 AACR.
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产品号#：
19158
19158RF
19053
19053RF
产品名：
EasySep™人CD8+ T细胞富集试剂盒
RoboSep™ 人CD8+ T细胞富集试剂盒含滤芯吸头
Hossain DMS et al. (AUG 2015)
Clinical cancer research : an official journal of the American Association for Cancer Research 21 16 3771--82
TLR9-Targeted STAT3 Silencing Abrogates Immunosuppressive Activity of Myeloid-Derived Suppressor Cells from Prostate Cancer Patients.
PURPOSE Recent advances in immunotherapy of advanced human cancers underscored the need to address and eliminate tumor immune evasion. The myeloid-derived suppressor cells (MDSC) are important inhibitors of T-cell responses in solid tumors,such as prostate cancers. However,targeting MDSCs proved challenging due to their phenotypic heterogeneity. EXPERIMENTAL DESIGN Myeloid cell populations were evaluated using flow cytometry on blood samples,functional assays,and immunohistochemical/immunofluorescent stainings on specimens from healthy subjects,localized and metastatic castration-resistant prostate cancer patients. RESULTS Here,we identify a population of Lin(-)CD15(HI)CD33(LO) granulocytic MDSCs that accumulate in patients' circulation during prostate cancer progression from localized to metastatic disease. The prostate cancer-associated MDSCs potently inhibit autologous CD8(+) T cells' proliferation and production of IFNγ and granzyme-B. The circulating MDSCs have high levels of activated STAT3,which is a central immune checkpoint regulator. The granulocytic pSTAT3(+) cells are also detectable in patients' prostate tissues. We previously generated an original strategy to silence genes specifically in Toll-like Receptor-9 (TLR9) positive myeloid cells using CpG-siRNA conjugates. We demonstrate that human granulocytic MDSCs express TLR9 and rapidly internalize naked CpG-STAT3siRNA,thereby silencing STAT3 expression. STAT3 blocking abrogates immunosuppressive effects of patients-derived MDSCs on effector CD8(+) T cells. These effects depended on reduced expression and enzymatic activity of Arginase-1,a downstream STAT3 target gene and a potent T-cell inhibitor. CONCLUSIONS Overall,we demonstrate the accumulation of granulocytic MDSCs with prostate cancer progression and the feasibility of using TLR9-targeted STAT3siRNA delivery strategy to alleviate MDSC-mediated immunosuppression.
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产品号#：
07933
07953
07949
产品名：
CryoStor®CS5
CryoStor®CS5
CryoStor®CS5
专家访谈
Payel Sil, PhD
Understanding the Role of Autophagy in Inflammation and Autoimmunity
研究方向：
免疫学
Topics：
The role of non-canonical autophagy on inflammation and autoimmunity
Immunoregulatory role of the LC3-associated phagocytosis (LAP) pathway
Sandrin V et al. (AUG 2002)
Blood 100 3 823--32
Lentiviral vectors pseudotyped with a modified RD114 envelope glycoprotein show increased stability in sera and augmented transduction of primary lymphocytes and CD34+ cells derived from human and nonhuman primates.
Generating lentiviral vectors pseudotyped with different viral glycoproteins (GPs) may modulate the physicochemical properties of the vectors,their interaction with the host immune system,and their host range. We have investigated the capacity of a panel of GPs of both retroviral (amphotropic murine leukemia virus [MLV-A]; gibbon ape leukemia virus [GALV]; RD114,feline endogenous virus) and nonretroviral (fowl plague virus [FPV]; Ebola virus [EboV]; vesicular stomatitis virus [VSV]; lymphocytic choriomeningitis virus [LCMV]) origins to pseudotype lentiviral vectors derived from simian immunodeficiency virus (SIVmac251). SIV vectors were efficiently pseudotyped with the FPV hemagglutinin,VSV-G,LCMV,and MLV-A GPs. In contrast,the GALV and RD114 GPs conferred much lower infectivity to the vectors. Capitalizing on the conservation of some structural features in the transmembrane domains and cytoplasmic tails of the incorporation-competent MLV-A GP and in RD114 and GALV GPs,we generated chimeric GPs encoding the extracellular and transmembrane domains of GALV or RD114 GPs fused to the cytoplasmic tail (designated TR) of MLV-A GP. Importantly,SIV-derived vectors pseudotyped with these GALV/TR and RD114/TR GP chimeras had significantly higher titers than vectors coated with the parental GPs. Additionally,RD114/TR-pseudotyped vectors were efficiently concentrated and were resistant to inactivation induced by the complement of both human and macaque sera,indicating that modified RD114 GP-pseudotyped lentiviral vectors may be of particular interest for in vivo gene transfer applications. Furthermore,as compared to vectors pseudotyped with other retroviral GPs or with VSV-G,RD114/TR-pseudotyped vectors showed augmented transduction of human and macaque primary blood lymphocytes and CD34+ cells.
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产品号#：
02690
09600
09650
产品名：
StemSpan™ CC100
StemSpan™ SFEM
StemSpan™ SFEM
Chang Q et al. (SEP 2002)
Infection and Immunity 70 9 4977--86
Structure-function relationships for human antibodies to pneumococcal capsular polysaccharide from transgenic mice with human immunoglobulin Loci.
To investigate the influence of antibody structure and specificity on antibody efficacy against Streptococcus pneumoniae,human monospecific antibodies (MAbs) to serotype 3 pneumococcal capsular polysaccharide (PPS-3) were generated from transgenic mice reconstituted with human immunoglobulin loci (XenoMouse mice) vaccinated with a PPS-3-tetanus toxoid conjugate and their molecular genetic structures,epitope specificities,and protective efficacies in normal and complement-deficient mice were determined. Nucleic acid sequence analysis of three MAbs (A7,1A2,and 7C5) revealed that they use two different V(H)3 genes (A7 and 1A2 both use V3-15) and three different V(kappa) gene segments. The MAbs were found to have similar affinities for PPS-3 but different epitope specificities and CDR3 regions. Both A7 and 7C5 had a lysine at the V(H)-D junction,whereas 1A2 had a threonine. Challenge experiments with serotype 3 S. pneumoniae in BALB/c mice revealed that both 10- and 1- micro g doses of A7 and 7C5 were protective,while only a 10- micro g dose of 1A2 was protective. Both A7 and 7C5 were also protective in mice lacking either an intact alternative (FB(-/-)) or classical (C4(-/-)) complement pathway,but 1A2 was not protective in either strain. Our data suggest that PPS-3 consists of epitopes that can elicit both highly protective and less protective antibodies and that the superior efficacies of certain antibodies may be a function of their structures and/or specificities. Further investigation of relationships between structure,specificity,and efficacy for defined MAbs to PPS may identify antibody features that might be useful surrogates for antibody (and vaccine) efficacy.
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EasySep™小鼠TIL（CD45）正选试剂盒
专家访谈Payel Sil, PhD Understanding the Role of Autophagy in Inflammation and Autoimmunity
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