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The TNF and TNF Receptor Review Superfamilies: Integrating Mammalian Biology
Cell, Vol. 104, 487±501, February 23, 2001, Copyright 2001 by Cell Press The TNF and TNF Receptor Review Superfamilies: Integrating Mammalian Biology Richard M. Locksley,*²³k Nigel Killeen,²k The receptors and ligands in this superfamily have and Michael J. Lenardo§k unique structural attributes that couple them directly to *Department of Medicine signaling pathways for cell proliferation, survival, and ² Department of Microbiology and Immunology differentiation. Thus, they have assumed prominent ³ Howard Hughes Medical Institute roles in the generation of tissues and transient microen- University of California, San Francisco vironments. Most TNF/TNFR SFPs are expressed in the San Francisco, California 94143 immune system, where their rapid and potent signaling § Laboratory of Immunology capabilities are crucial in coordinating the proliferation National Institute of Allergy and Infectious Diseases and protective functions of pathogen-reactive cells. National Institutes of Health Here, we review the organization of the TNF/TNFR SF Bethesda, Maryland 20892 and how these proteins have been adapted for pro- cesses as seemingly disparate as host defense and or- ganogenesis. In interpreting this large and highly active Introduction area of research, we have focused on common themes that unite the actions of these genes in different tissues. Three decades ago, lymphotoxin (LT) and tumor necro- We also discuss the evolutionary success of this super- sis factor (TNF) were identified as products of lympho- familyÐsuccess that we infer from its expansion across cytes and macrophages that caused the lysis of certain the mammalian genome and from its many indispens- types of cells, especially tumor cells (Granger et al., able roles in mammalian biology. -
Human and Mouse CD Marker Handbook Human and Mouse CD Marker Key Markers - Human Key Markers - Mouse
Welcome to More Choice CD Marker Handbook For more information, please visit: Human bdbiosciences.com/eu/go/humancdmarkers Mouse bdbiosciences.com/eu/go/mousecdmarkers Human and Mouse CD Marker Handbook Human and Mouse CD Marker Key Markers - Human Key Markers - Mouse CD3 CD3 CD (cluster of differentiation) molecules are cell surface markers T Cell CD4 CD4 useful for the identification and characterization of leukocytes. The CD CD8 CD8 nomenclature was developed and is maintained through the HLDA (Human Leukocyte Differentiation Antigens) workshop started in 1982. CD45R/B220 CD19 CD19 The goal is to provide standardization of monoclonal antibodies to B Cell CD20 CD22 (B cell activation marker) human antigens across laboratories. To characterize or “workshop” the antibodies, multiple laboratories carry out blind analyses of antibodies. These results independently validate antibody specificity. CD11c CD11c Dendritic Cell CD123 CD123 While the CD nomenclature has been developed for use with human antigens, it is applied to corresponding mouse antigens as well as antigens from other species. However, the mouse and other species NK Cell CD56 CD335 (NKp46) antibodies are not tested by HLDA. Human CD markers were reviewed by the HLDA. New CD markers Stem Cell/ CD34 CD34 were established at the HLDA9 meeting held in Barcelona in 2010. For Precursor hematopoetic stem cell only hematopoetic stem cell only additional information and CD markers please visit www.hcdm.org. Macrophage/ CD14 CD11b/ Mac-1 Monocyte CD33 Ly-71 (F4/80) CD66b Granulocyte CD66b Gr-1/Ly6G Ly6C CD41 CD41 CD61 (Integrin b3) CD61 Platelet CD9 CD62 CD62P (activated platelets) CD235a CD235a Erythrocyte Ter-119 CD146 MECA-32 CD106 CD146 Endothelial Cell CD31 CD62E (activated endothelial cells) Epithelial Cell CD236 CD326 (EPCAM1) For Research Use Only. -
Single-Cell RNA Sequencing Demonstrates the Molecular and Cellular Reprogramming of Metastatic Lung Adenocarcinoma
ARTICLE https://doi.org/10.1038/s41467-020-16164-1 OPEN Single-cell RNA sequencing demonstrates the molecular and cellular reprogramming of metastatic lung adenocarcinoma Nayoung Kim 1,2,3,13, Hong Kwan Kim4,13, Kyungjong Lee 5,13, Yourae Hong 1,6, Jong Ho Cho4, Jung Won Choi7, Jung-Il Lee7, Yeon-Lim Suh8,BoMiKu9, Hye Hyeon Eum 1,2,3, Soyean Choi 1, Yoon-La Choi6,10,11, Je-Gun Joung1, Woong-Yang Park 1,2,6, Hyun Ae Jung12, Jong-Mu Sun12, Se-Hoon Lee12, ✉ ✉ Jin Seok Ahn12, Keunchil Park12, Myung-Ju Ahn 12 & Hae-Ock Lee 1,2,3,6 1234567890():,; Advanced metastatic cancer poses utmost clinical challenges and may present molecular and cellular features distinct from an early-stage cancer. Herein, we present single-cell tran- scriptome profiling of metastatic lung adenocarcinoma, the most prevalent histological lung cancer type diagnosed at stage IV in over 40% of all cases. From 208,506 cells populating the normal tissues or early to metastatic stage cancer in 44 patients, we identify a cancer cell subtype deviating from the normal differentiation trajectory and dominating the metastatic stage. In all stages, the stromal and immune cell dynamics reveal ontological and functional changes that create a pro-tumoral and immunosuppressive microenvironment. Normal resident myeloid cell populations are gradually replaced with monocyte-derived macrophages and dendritic cells, along with T-cell exhaustion. This extensive single-cell analysis enhances our understanding of molecular and cellular dynamics in metastatic lung cancer and reveals potential diagnostic and therapeutic targets in cancer-microenvironment interactions. 1 Samsung Genome Institute, Samsung Medical Center, Seoul 06351, Korea. -
Human TNFRSF18 ELISA Kit (ARG81453)
Product datasheet [email protected] ARG81453 Package: 96 wells Human TNFRSF18 ELISA Kit Store at: 4°C Component Cat. No. Component Name Package Temp ARG81453-001 Antibody-coated 8 X 12 strips 4°C. Unused strips microplate should be sealed tightly in the air-tight pouch. ARG81453-002 Standard 2 X 10 ng/vial 4°C ARG81453-003 Standard/Sample 30 ml (Ready to use) 4°C diluent ARG81453-004 Antibody conjugate 1 vial (100 µl) 4°C concentrate (100X) ARG81453-005 Antibody diluent 12 ml (Ready to use) 4°C buffer ARG81453-006 HRP-Streptavidin 1 vial (100 µl) 4°C concentrate (100X) ARG81453-007 HRP-Streptavidin 12 ml (Ready to use) 4°C diluent buffer ARG81453-008 25X Wash buffer 20 ml 4°C ARG81453-009 TMB substrate 10 ml (Ready to use) 4°C (Protect from light) ARG81453-010 STOP solution 10 ml (Ready to use) 4°C ARG81453-011 Plate sealer 4 strips Room temperature Summary Product Description ARG81453 Human TNFRSF18 ELISA Kit is an Enzyme Immunoassay kit for the quantification of Human TNFRSF18 in serum, plasma (heparin, EDTA) and cell culture supernatants. Tested Reactivity Hu Tested Application ELISA Specificity There is no detectable cross-reactivity with other relevant proteins. Target Name TNFRSF18 Conjugation HRP Conjugation Note Substrate: TMB and read at 450 nm. Sensitivity 31.25 pg/ml Sample Type Serum, plasma (heparin, EDTA) and cell culture supernatants. Standard Range 62.5 - 4000 pg/ml Sample Volume 100 µl www.arigobio.com 1/3 Precision Intra-Assay CV: 6.3% Inter-Assay CV: 7.0% Alternate Names Tumor necrosis factor receptor superfamily member 18; AITR; CD357; CD antigen CD357; Activation- inducible TNFR family receptor; GITR-D; GITR; Glucocorticoid-induced TNFR-related protein Application Instructions Assay Time ~ 5 hours Properties Form 96 well Storage instruction Store the kit at 2-8°C. -
CD45) 6 7 8 9 10 11 12 13 Melissa L
bioRxiv preprint doi: https://doi.org/10.1101/2020.09.29.318709; this version posted September 29, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. 1 2 3 4 5 The roseoloviruses downregulate the protein tyrosine phosphatase PTPRC (CD45) 6 7 8 9 10 11 12 13 Melissa L. Whyte1, Kelsey Smith1, Amanda Buchberger2,4, Linda Berg Luecke 4, Lidya 14 Handayani Tjan3, Yasuko Mori3, Rebekah L Gundry2,4, and Amy W. Hudson1# 15 16 17 18 19 20 21 22 23 24 25 26 27 1: Department of Microbiology and Immunology, Medical College of Wisconsin, Milwaukee, WI 28 2. Department of Biochemistry, Medical College of Wisconsin, Milwaukee, WI 29 3. Division of Clinical Virology, Kobe University Graduate School of Medicine, Kobe, Japan 30 4: Current address: CardiOmics Program, Center for Heart and Vascular Research; Division of 31 Cardiovascular Medicine; and Department of Cellular and Integrative Physiology, University of 32 Nebraska Medical Center, Omaha, NE 33 34 35 36 #To whom correspondence should be addressed: [email protected] 37 38 39 40 Runnning title: Roseolovirus downregulation of CD45 41 42 43 44 45 46 1 bioRxiv preprint doi: https://doi.org/10.1101/2020.09.29.318709; this version posted September 29, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. 47 Abstract 48 Like all herpesviruses, the roseoloviruses (HHV6A, -6B, and -7) establish lifelong 49 infection within their host, requiring these viruses to evade host anti-viral responses. -
TNFRSF18 (Human) ELISA Kit
TNFRSF18 (Human) ELISA Kit Catalog Number KA1720 96 assays Version: 01 Intended for research use only www.abnova.com I. INTRODUCTION GITR (glucocorticoid induced tumor necrosis factor receptor family related gene) is a type-1 transmembrane protein of 228 amino acids belonging to the TNF and NGF receptor family of proteins. GITR is expressed in normal T-lymphocytes from thymus, spleen. Constitutive expression of a transfected GITR gene induces resistance to apoptosis induced by anti CD3 monoclonal antibodies. The human homolog of GITR is expressed in lymph node and peripheral blood leukocytes. Its expression is up-regulated in human peripheral mononuclear cells mainly after stimulation with antibodies against CD3 and CD28. TNFRSF18 (Human) ELISA Kit is an in vitro enzyme-linked immunosorbent assay for the quantitative measurement of human GITR in cell lysate and tissue lysate. This assay employs an antibody specific for human GITR coated on a 96-well plate. Standards and samples are pipetted into the wells and GITR present in a sample is bound to the wells by the immobilized antibody. The wells are washed and biotinylated anti-human GITR antibody is added. After washing away unbound biotinylated antibody, HRP-conjugated streptavidin is pipetted to the wells. The wells are again washed, a TMB substrate solution is added to the wells and color develops in proportion to the amount of GITR bound. The Stop Solution changes the color from blue to yellow, and the intensity of the color is measured at 450 nm. II. REAGENTS 1. GITR Microplate (Item A): 96 wells (12 strips x 8 wells) coated with anti-human GITR. -
Supplemental Figures and Figure Legends
Supplemental Figures and Figure Legends A Source Hirst REMC 1 Source Hirst REMC Source Hirst Source 1 0.9 0.8 0.7 0.6 0.9 REMC 1 0.9 0.8 0.7 0.6 Source Source B Penis_Foreskin_Melanocyte_Primary_Cells_skin03 Penis_Foreskin_Melanocyte_Primary_Cells_skin01 Penis_Foreskin_Melanocyte_Primary_Cells_skin03 0.8HUVEC Penis_Foreskin_Melanocyte_Primary_Cells_skin01 Penis_Foreskin_Fibroblast_Primary_Cells_skin02 Penis_Foreskin_Fibroblast_Primary_Cells_skin01 HUVEC H1_Derived_Mesenchymal_Stem_Cells Penis_Foreskin_Fibroblast_Primary_Cells_skin02 NHLF 0.7HSMM Penis_Foreskin_Fibroblast_Primary_Cells_skin01 Universal_Human_Reference H1_Derived_Mesenchymal_Stem_Cells NHEK Breast_vHMEC NHLF HMEC HSMM Penis_Foreskin_Keratinocyte_Primary_Cells_skin03 0.6Penis_Foreskin_Keratinocyte_Primary_Cells_skin02 Universal_Human_Reference Breast_Myoepithelial_Cells NHEK HELA A549 Breast_vHMEC HEPG2 HMEC hESC_Derived_CD56+_Mesoderm_Cultured_Cells H1_BMP4_Derived_Trophoblast_Cultured_Cells Penis_Foreskin_Keratinocyte_Primary_Cells_skin03 HUES64_Cell_Line Penis_Foreskin_Keratinocyte_Primary_Cells_skin02 H1_BMP4_Derived_Mesendoderm_Cultured_Cells Breast_Myoepithelial_Cells 4star H1_Cell_Line HELA hESC_Derived_CD56+_Ectoderm_Cultured_Cells A549 H1_Derived_Neuronal_Progenitor_Cultured_Cells hESC_Derived_CD184+_Endoderm_Cultured_Cells HEPG2 Neurosphere_Cultured_Cells_Ganglionic_Eminence_Derived hESC_Derived_CD56+_Mesoderm_Cultured_Cells Neurosphere_Cultured_Cells_Cortex_Derived Brain_Germinal_Matrix H1_BMP4_Derived_Trophoblast_Cultured_Cells Fetal_Brain_Female HUES64_Cell_Line -
Protein Tyrosine Phosphatase Receptor Type C (PTPRC Or CD45)
Molecules in pathogenesis Protein tyrosine phosphatase receptor type C (PTPRC J Clin Pathol: first published as 10.1136/jclinpath-2020-206927 on 26 May 2021. Downloaded from or CD45) Maryam Ahmed Al Barashdi ,1 Ahlam Ali,1 Mary Frances McMullin ,2 Ken Mills1 1Patrick G Johnston Centre for ABSTRACT The extracellular portion of the CD45 consists of Cancer Research (PGJCCR), The leucocyte common antigen, protein tyrosine five regions (figure 1). The extended N-terminal Queen’s University Belfast, region has alternatively spliced exons, with several Belfast, UK phosphatase receptor type C (PTPRC), also known as 2Haematology, Belfast City CD45, is a transmembrane glycoprotein, expressed regions for O- linked glycosylation and thus form Hospital, Belfast, UK on almost all haematopoietic cells except for mature the protein variable area. All species have a similar erythrocytes, and is an essential regulator of T and B structure of the CD45 extracellular domain, the Correspondence to cell antigen receptor-mediated activation. Disruption three membrane- proximal portion and the type III Maryam Ahmed Al Barashdi, of the equilibrium between protein tyrosine kinase and fibronectin (FnIII) domain. In mammals, between Medicine, Queen’s University the O- glycan tract and FnIII domains, a globular Belfast, Belfast BT7 1NN, UK; phosphatase activity (from CD45 and others) can result malbarashdi01@ qub. ac. uk in immunodeficiency, autoimmunity, or malignancy. domain exists with five conserved cysteine- rich CD45 is normally present on the cell surface, therefore domains (figure 1).4 Received 3 August 2020 it works upstream of a large signalling network which The CD45 gene, protein tyrosine phosphatase Accepted 16 February 2021 differs between cell types, and thus the effects of CD45 receptor type C (PTPRC), consists of 35 exons, four on these cells are also different. -
Single-Cell Transcriptome Profiling of the Kidney Glomerulus Identifies Key Cell Types and Reactions to Injury
BASIC RESEARCH www.jasn.org Single-Cell Transcriptome Profiling of the Kidney Glomerulus Identifies Key Cell Types and Reactions to Injury Jun-Jae Chung ,1 Leonard Goldstein ,2 Ying-Jiun J. Chen,2 Jiyeon Lee ,1 Joshua D. Webster,3 Merone Roose-Girma,2 Sharad C. Paudyal,4 Zora Modrusan,2 Anwesha Dey,5 and Andrey S. Shaw1 Due to the number of contributing authors, the affiliations are listed at the end of this article. ABSTRACT Background The glomerulus is a specialized capillary bed that is involved in urine production and BP control. Glomerular injury is a major cause of CKD, which is epidemic and without therapeutic options. Single-cell transcriptomics has radically improved our ability to characterize complex organs, such as the kidney. Cells of the glomerulus, however, have been largely underrepresented in previous single-cell kidney studies due to their paucity and intractability. Methods Single-cell RNA sequencing comprehensively characterized the types of cells in the glomerulus from healthy mice and from four different disease models (nephrotoxic serum nephritis, diabetes, doxo- rubicin toxicity, and CD2AP deficiency). Results Allcelltypesintheglomeruluswereidentified using unsupervised clustering analysis. Novel marker genes and gene signatures of mesangial cells, vascular smooth muscle cells of the afferent and efferent arteri- oles, parietal epithelial cells, and three types of endothelial cells were identified. Analysis of the disease models revealed cell type–specific and injury type–specific responses in the glomerulus, including acute activation of the Hippo pathway in podocytes after nephrotoxic immune injury. Conditional deletion of YAP or TAZ resulted in more severe and prolonged proteinuria in response to injury, as well as worse glomerulosclerosis. -
Supplementary Tables
Supplementary Table 1 Lymphocyte activation Activation of immune response Cell adhesion Rank Gene p-value Fold change Rank Gene p-value Fold change Rank Gene p-value Fold change 1 BATF 0.00001 6.31564 1 DUSP6 0.00002 6.39359 1 IL21 0.00014 8.20000 2 MIF 0.00007 2.68925 2 TANK 0.00020 1.69235 2 IL2RA 0.00037 7.70668 3 NFATC2 0.00008 0.40405 3 IRAK1 0.00057 1.63217 3 C1QBP 0.00039 3.79258 4 INPP5D 0.00028 0.31780 4 CHUK 0.00080 1.59486 4 CCL28 0.00010 2.43756 5 TNFSF12 0.00002 0.30456 5 HRAS 0.00004 1.58111 5 BCL10 0.00036 0.62896 6 CASP8 0.00001 0.23611 6 CREB1 0.00037 0.58528 6 IRF1 0.00027 0.62762 7 SMAD3 0.00002 0.23043 7 CD3E 0.00023 0.49823 7 CD46 0.00033 0.52342 8 RORA 0.00001 0.14902 8 ZAP70 0.00068 0.46392 8 SPN 0.00022 0.48806 9 CTSS 0.00024 0.30270 9 JAK2 0.00086 0.45576 10 PLA2G6 0.00002 0.22338 10 TGFB1 0.00006 0.44888 11 TLR3 0.00045 0.13067 11 IL12RB1 0.00021 0.39881 12 ITGA4 0.00098 0.37128 13 ITGAL 0.00013 0.32985 14 CCR2 0.00049 0.29760 15 CD44 0.00097 0.21387 Supplementary Table 1. Differentially expressed genes (p<0.05) in CAR compared to delta CAR T cells. The table displays the p-values and fold changes of genes that are differentially regulated in CAR T cells compared to the truncated CAR (ΔCAR) control T cells collected 24 hours post-stimulation with PSCA. -
Human GITR/TNFRSF18 Alexa Fluor® 700-Conjugated Antibody
Human GITR/TNFRSF18 Alexa Fluor® 700-conjugated Antibody Monoclonal Mouse IgG1 Clone # 110416 Catalog Number: FAB689N 100 Tests, 25 Tests DESCRIPTION Species Reactivity Human Specificity Detects human GITR in direct ELISAs and Western blots. Does not crossreact with recombinant human (rh) 41BB, recombinant mouse (rm) 41BB, rhCD27, rmCD27, rhCD30, rmCD30, rhCD40, rmCD40, rhDR3, rhDR6, rhEDAR, rmEDAR, rhFas, rmFAS, rmGITR, rhHVEM, rhLymphotoxin Rβ, rmLymphotoxin Rβ, rhNGF R, rhOPG, rmOPG, rhRANK, rmRANK, rhTAJ, rhTNF RI, rmTNF RI, rhTNF RII, or rmTNF RII. Source Monoclonal Mouse IgG1 Clone # 110416 Purification Protein A or G purified from hybridoma culture supernatant Immunogen Mouse myeloma cell line NS0derived recombinant human GITR/TNFRSF18 Gln26Glu161 (Thr43Ala) Accession # Q9Y5U5 Conjugate Alexa Fluor 700 Excitation Wavelength: 675700 nm Emission Wavelength: 723 nm Formulation Supplied in a saline solution containing BSA and Sodium Azide. See Certificate of Analysis for details. *Contains <0.1% Sodium Azide, which is not hazardous at this concentration according to GHS classifications. Refer to the Safety Data Sheet (SDS) for additional information and handling instructions. APPLICATIONS Please Note: Optimal dilutions should be determined by each laboratory for each application. General Protocols are available in the Technical Information section on our website. Recommended Sample Concentration Flow Cytometry 5 µL/106 cells See Below DATA Flow Cytometry Detection of GITR/TNFRSF18 in Human PBMCs by Flow Cytometry. Human peripheral blood mononuclear cells (PBMCs) treated with 5 μg/mL PHA for 5 days were stained with Mouse Anti Human CD4 PEconjugated Monoclonal Antibody (Catalog # FAB3791P) and either (A) Mouse AntiHuman GITR/TNFRSF18 Alexa Fluor® 700conjugated Monoclonal Antibody (Catalog # FAB689N) or (B) Mouse IgG1 Alexa Fluor 700 Isotype Control (Catalog # IC002N). -
KRAS Mutations Are Negatively Correlated with Immunity in Colon Cancer
www.aging-us.com AGING 2021, Vol. 13, No. 1 Research Paper KRAS mutations are negatively correlated with immunity in colon cancer Xiaorui Fu1,2,*, Xinyi Wang1,2,*, Jinzhong Duanmu1, Taiyuan Li1, Qunguang Jiang1 1Department of Gastrointestinal Surgery, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, People's Republic of China 2Queen Mary College, Medical Department, Nanchang University, Nanchang, Jiangxi, People's Republic of China *Equal contribution Correspondence to: Qunguang Jiang; email: [email protected] Keywords: KRAS mutations, immunity, colon cancer, tumor-infiltrating immune cells, inflammation Received: March 27, 2020 Accepted: October 8, 2020 Published: November 26, 2020 Copyright: © 2020 Fu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. ABSTRACT The heterogeneity of colon cancer tumors suggests that therapeutics targeting specific molecules may be effective in only a few patients. It is therefore necessary to explore gene mutations in colon cancer. In this study, we obtained colon cancer samples from The Cancer Genome Atlas, and the International Cancer Genome Consortium. We evaluated the landscape of somatic mutations in colon cancer and found that KRAS mutations, particularly rs121913529, were frequent and had prognostic value. Using ESTIMATE analysis, we observed that the KRAS-mutated group had higher tumor purity, lower immune score, and lower stromal score than the wild- type group. Through single-sample Gene Set Enrichment Analysis and Gene Set Enrichment Analysis, we found that KRAS mutations negatively correlated with enrichment levels of tumor infiltrating lymphocytes, inflammation, and cytolytic activities.