Search results for: Interferon γ
#33651510 
2021/02/18
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[A man with erythematosquamous plaques].
A 43-year-old male visited our dermatology department with a skin eruption diagnosed as psoriasis. It began 1 month after starting peg-interferon-α-1a therapy for multiple sclerosis. Peg-interferon is known to be able to induce psoriasis, as well as other medication, while the pathophysiology remains unclear.Y C Weng, F Bruynzeel
2175 related Products with: [A man with erythematosquamous plaques].
1 mg10 mg5 mg96-well plate X 2 100ul1 mg10 mg 25 GBox of 20 tubes100 mg25 mg250 mg
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#33651101 //
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Proteomic and bioinformatic profiling of neutrophils in CLL reveals functional defects that predispose to bacterial infections.
Patients with chronic lymphocytic leukemia (CLL) typically suffer from frequent and severe bacterial infections. Although it is well known that neutrophils are critical innate immune cells facilitating the early defense, the underlying phenotypical and functional changes in neutrophils during CLL remain largely elusive. Using a murine adoptive transfer model of CLL, we demonstrate aggravated bacterial burden in CLL-bearing mice upon a urinary tract infection with uropathogenic Escherichia coli. Bioinformatic analyses of the neutrophil proteome revealed increased expression of proteins associated with interferon signaling and decreased protein expression associated with granule composition and neutrophil migration. Functional experiments validated these findings by showing reduced levels of myeloperoxidase and acidification of neutrophil granules after ex vivo phagocytosis of bacteria. Pathway enrichment analysis indicated decreased expression of molecules critical for neutrophil recruitment, and migration of neutrophils into the infected urinary bladder was significantly reduced. These altered migratory properties of neutrophils were also associated with reduced expression of CD62L and CXCR4 and correlated with an increased incidence of infections in patients with CLL. In conclusion, this study describes a molecular signature of neutrophils through proteomic, bioinformatic, and functional analyses that are linked to a reduced migratory ability, potentially leading to increased bacterial infections in patients with CLL.Nirojah Subramaniam, Jenny Bottek, Stephanie Thiebes, Kristina Zec, Matthias Kudla, Camille Soun, Elena de Dios Panal, Julia K Lill, Aaron Pfennig, Ralf Herrmann, Kirsten Bruderek, Sven Rahmann, Sven Brandau, Patricia Johansson, Hans Christian Reinhardt, Jan Dürig, Martina Seiffert, Thilo Bracht, Barbara Sitek, Daniel Robert Engel
1405 related Products with: Proteomic and bioinformatic profiling of neutrophils in CLL reveals functional defects that predispose to bacterial infections.
25 1096 wells100 1 kit(96 Wells)1 mg
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#33650815 2021/03/01
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Immunomodulatory Activity of Human Bone Marrow and Adipose-Derived Mesenchymal Stem Cells Prolongs Allogenic Skin Graft Survival in Nonhuman Primates.
In the present study, we examined the tolerance-inducing effects of human adipose-derived mesenchymal stem cells (hAD-MSCs) and bone marrow-derived MSCs (hBM-MSCs) on a nonhuman primate model of skin transplantation.Fattah Sotoodehnejadnematalahi, Reza Moghadasali, Mostafa Hajinasrollah, Ehsan Ehsani, Ensiyeh Hajizadeh-Saffar, Niloofar Sodeifi, Reza Saidi, Morteza Zarrabi, Mohammad Farzanehkhah, Bahareh Sadeghi, Hossein Baharvand, Nasser Aghdami
2317 related Products with: Immunomodulatory Activity of Human Bone Marrow and Adipose-Derived Mesenchymal Stem Cells Prolongs Allogenic Skin Graft Survival in Nonhuman Primates.
10 ug1 mg1.00 flask1.00 flask96T1.00 flask900 tests1.00 flask4 x 96-well plate
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#33650635 2021/03/02
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Elucidating the role of GRIM-19 as a substrate and allosteric activator of pro-apoptotic serine protease HtrA2.
HtrA2 (High-temperature requirement A2) and GRIM-19 (Gene associated with retinoic and interferon-induced mortality 19 protein) are involved in various biological functions with their deregulation leading to multiple diseases. Although it is known that the interaction between GRIM-19 with HtrA2 promotes pro-apoptotic activity of the latter, the mechanistic details remained elusive till date. Moreover, designing allosteric modulators of HtrA2 remains obscure due to lack of adequate information on the mode of interaction with its natural substrates cum binding partners. Therefore, in this study, we have unfolded the interaction between HtrA2 and GRIM-19 so as to understand its subsequent functional repercussions. Using in silico analyses and biochemical assays, we identified the region in GRIM-19 that is involved in protein-protein interaction with HtrA2. Furthermore, we have presented a comprehensive illustration of HtrA2's cleavage site specificity. Quantitative analysis using enzyme kinetics underscored the role of GRIM-19 in significant allosteric activation of HtrA2. Overall, this is an extensive study that not only defines HtrA2-GRIM-19 interaction, but also creates a framework for developing strategies toward allosteric regulation of HtrA2 for future therapeutic interventions.Raghupathi Kummari, Shubhankar Dutta, Shubhangi Patil, Snehal Pandav Mudrale, Kakoli Bose
1048 related Products with: Elucidating the role of GRIM-19 as a substrate and allosteric activator of pro-apoptotic serine protease HtrA2.
9 x 25 assays1000 assays1000 assays200 assays200 assays1000 assays200 assays200 assays100ug200 assays50 assays1000 assays
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#33649782 2021/03/02
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Rs41291957 polymorphism in the promoter region of microRNA‑143 serves as a prognostic biomarker for patients with intracranial hemorrhage.
The present study aimed to investigate the function of the single nucleotide polymorphism (SNP) rs41291957 in the prognosis of intracerebral hemorrhage (ICH). In addition, the molecular mechanisms underlying the role of microRNA (miR)‑143, Toll‑like receptor 2 (TLR2) and interleukin‑16 (IL‑16) were studied in patients with ICH that carried different alleles in the locus of the rs41291957 SNP. Kaplan‑Meier survival curves were calculated for 182 patients with ICH, genotyped as CC, presenting a cytosine in both chromosome, CT, presenting both variants, and TT, presents a thymine in both chromosomes. In addition, the possible regulatory relationships between miR‑143 and TLR2/IL‑16 were studied using computational analysis, luciferase assays and western blot assay. In addition, the inflammatory profiles of cerebrospinal fluid (CSF) and serum samples collected from the subjects were compared. The patients genotyped as TT presented the lowest survival rate, while patients genotyped as CC presented the highest survival rate. TLR2 mRNA was identified as a potential target of miR‑143, while IL‑16 showed no direct interaction with miR‑143. The above regulatory relationships were further investigated using cells transfected with miR‑143 precursor or TLR2 small interfering RNA. In addition, the expression levels of inflammatory factors, such as tumor necrosis factor α, interferon, IL‑6, IL‑10 and NF‑L‑6, were highest in the CSF/serum samples collected from patients genotyped as TT and lowest in patients genotyped as CC. By contrast, the expression levels of miR‑143 showed an opposite trend in the expression of the above inflammatory factors. The rs41291957 SNP, located in the promoter region of miR‑143, reduced the expression of miR‑143 and upregulated the expression of the pro‑inflammatory factor TLR2, eventually leading to a poorer prognosis in patients with ICH.Xiaobo Yang, Zongduo Guo, Fang Cao, Zhipeng Teng, Zhijian Huang, Xiaochuan Sun
1729 related Products with: Rs41291957 polymorphism in the promoter region of microRNA‑143 serves as a prognostic biomarker for patients with intracranial hemorrhage.
100 μg100 μg100 μg100 μg100 μg100 μg100 μg100 μg100 μg100 μg96 samples100 μg
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#33649593 2021/03/01
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Characterizing the molecular regulation of inhibitory immune checkpoints with multimodal single-cell screens.
The expression of inhibitory immune checkpoint molecules, such as programmed death-ligand (PD-L)1, is frequently observed in human cancers and can lead to the suppression of T cell-mediated immune responses. Here, we apply expanded CRISPR-compatible (EC)CITE-seq, a technology that combines pooled CRISPR screens with single-cell mRNA and surface protein measurements, to explore the molecular networks that regulate PD-L1 expression. We also develop a computational framework, mixscape, that substantially improves the signal-to-noise ratio in single-cell perturbation screens by identifying and removing confounding sources of variation. Applying these tools, we identify and validate regulators of PD-L1 and leverage our multimodal data to identify both transcriptional and post-transcriptional modes of regulation. Specifically, we discover that the Kelch-like protein KEAP1 and the transcriptional activator NRF2 mediate the upregulation of PD-L1 after interferon (IFN)-γ stimulation. Our results identify a new mechanism for the regulation of immune checkpoints and present a powerful analytical framework for the analysis of multimodal single-cell perturbation screens.Efthymia Papalexi, Eleni P Mimitou, Andrew W Butler, Samantha Foster, Bernadette Bracken, William M Mauck, Hans-Hermann Wessels, Yuhan Hao, Bertrand Z Yeung, Peter Smibert, Rahul Satija
1381 related Products with: Characterizing the molecular regulation of inhibitory immune checkpoints with multimodal single-cell screens.
200 units200 units2 Pieces/Box5 x 50 ug96 wells50 ug5 x 50 Pieces/case 200 Tests250 ml.1 kit(96 Wells)
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#33649592 2021/03/01
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Multimodal pooled Perturb-CITE-seq screens in patient models define mechanisms of cancer immune evasion.
Resistance to immune checkpoint inhibitors (ICIs) is a key challenge in cancer therapy. To elucidate underlying mechanisms, we developed Perturb-CITE-sequencing (Perturb-CITE-seq), enabling pooled clustered regularly interspaced short palindromic repeat (CRISPR)-Cas9 perturbations with single-cell transcriptome and protein readouts. In patient-derived melanoma cells and autologous tumor-infiltrating lymphocyte (TIL) co-cultures, we profiled transcriptomes and 20 proteins in ~218,000 cells under ~750 perturbations associated with cancer cell-intrinsic ICI resistance (ICR). We recover known mechanisms of resistance, including defects in the interferon-γ (IFN-γ)-JAK/STAT and antigen-presentation pathways in RNA, protein and perturbation space, and new ones, including loss/downregulation of CD58. Loss of CD58 conferred immune evasion in multiple co-culture models and was downregulated in tumors of melanoma patients with ICR. CD58 protein expression was not induced by IFN-γ signaling, and CD58 loss conferred immune evasion without compromising major histocompatibility complex (MHC) expression, suggesting that it acts orthogonally to known mechanisms of ICR. This work provides a framework for the deciphering of complex mechanisms by large-scale perturbation screens with multimodal, single-cell readouts, and discovers potentially clinically relevant mechanisms of immune evasion.Chris J Frangieh, Johannes C Melms, Pratiksha I Thakore, Kathryn R Geiger-Schuller, Patricia Ho, Adrienne M Luoma, Brian Cleary, Livnat Jerby-Arnon, Shruti Malu, Michael S Cuoco, Maryann Zhao, Casey R Ager, Meri Rogava, Lila Hovey, Asaf Rotem, Chantale Bernatchez, Kai W Wucherpfennig, Bruce E Johnson, Orit Rozenblatt-Rosen, Dirk Schadendorf, Aviv Regev, Benjamin Izar
1560 related Products with: Multimodal pooled Perturb-CITE-seq screens in patient models define mechanisms of cancer immune evasion.
5mg5mg
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#33649580 2021/03/01
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Effector and stem-like memory cell fates are imprinted in distinct lymph node niches directed by CXCR3 ligands.
T cells dynamically interact with multiple, distinct cellular subsets to determine effector and memory differentiation. Here, we developed a platform to quantify cell location in three dimensions to determine the spatial requirements that direct T cell fate. After viral infection, we demonstrated that CD8 effector T cell differentiation is associated with positioning at the lymph node periphery. This was instructed by CXCR3 signaling since, in its absence, T cells are confined to the lymph node center and alternatively differentiate into stem-like memory cell precursors. By mapping the cellular sources of CXCR3 ligands, we demonstrated that CXCL9 and CXCL10 are expressed by spatially distinct dendritic and stromal cell subsets. Unlike effector cells, retention of stem-like memory precursors in the paracortex is associated with CCR7 expression. Finally, we demonstrated that T cell location can be tuned, through deficiency in CXCL10 or type I interferon signaling, to promote effector or stem-like memory fates.Brigette C Duckworth, Fanny Lafouresse, Verena C Wimmer, Benjamin J Broomfield, Lennard Dalit, Yannick O Alexandre, Amania A Sheikh, Raymond Z Qin, Carolina Alvarado, Lisa A Mielke, Marc Pellegrini, Scott N Mueller, Thomas Boudier, Kelly L Rogers, Joanna R Groom
2867 related Products with: Effector and stem-like memory cell fates are imprinted in distinct lymph node niches directed by CXCR3 ligands.
3 inhibitorscase10 ugcase1 L.
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#33649314 2021/03/01
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Relapsed multiple myeloma demonstrates distinct patterns of immune microenvironment and malignant cell-mediated immunosuppression.
Immunotherapy has shown efficacy in relapsed multiple myeloma (MM). However, these therapies may depend on a functional tumor immune microenvironment (iTME) for their efficacy. Characterizing the evolution of the iTME over the disease course is necessary to optimize the timing of immunotherapies. We performed mass cytometry, cytokine analysis, and RNA sequencing on bone marrow samples from 39 (13 newly diagnosed [NDMM], 11 relapsed pre-daratumumab exposure [RMM], and 13 triple-refractory [TRMM]) MM patients. Three distinct cellular iTME clusters were identified; cluster 1 comprised mainly of NDMM and RMM patients; and clusters 2 and 3 comprised primarily of TRMM patients. We showed that naive T cells were decreased in clusters 2 and 3, cluster 2 was characterized by increased senescent T cells, and cluster 3 by decreased early memory T cells. Plasma cells in clusters 2 and 3 upregulated E2F transcription factors and MYC proliferation pathways, and downregulated interferon, TGF-beta, interleuking-6, and TNF-αlpha signaling pathways compared to cluster 1. This study suggests that the MM iTME becomes increasingly dysfunctional with therapy whereas the MM clone may be less dependent on inflammation-mediated growth pathways and less sensitive to IFN-mediated immunosurveillance. Our findings may explain the decreased sensitivity of TRMM patients to novel immunotherapies.Alissa Visram, Surendra Dasari, Emilie Anderson, Shaji Kumar, Taxiarchis V Kourelis
1436 related Products with: Relapsed multiple myeloma demonstrates distinct patterns of immune microenvironment and malignant cell-mediated immunosuppression.
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