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https://www.readbyqxmd.com/read/28526333/systemic-manifestations-of-primary-sj%C3%A3-gren-s-syndrome-in-the-nod-b10sn-h2-b-j-mouse-model
#1
Jeremy Kiripolsky, Long Shen, Yichen Liang, Alisa Li, Lakshmanan Suresh, Yun Lian, Quan-Zhen Li, Daniel P Gaile, Jill M Kramer
Animal models that recapitulate human disease are crucial for the study of Sjögren's Syndrome (SS). While several SS mouse models exist, there are few primary SS (pSS) models that mimic systemic disease manifestations seen in humans. Similar to pSS patients, NOD.B10Sn-H2(b)/J (NOD.B10) mice develop exocrine gland disease and anti-nuclear autoantibodies. However, the disease kinetics and spectrum of extra-glandular disease remain poorly characterized in this model. Our objective was to characterize local and systemic SS manifestations in depth in NOD...
May 16, 2017: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/28511686/intrathymic-injection-of-hematopoietic-progenitor-cells-establishes-functional-t-cell-development-in-a-mouse-model-of-severe-combined-immunodeficiency
#2
Andrea Z Tuckett, Raymond H Thornton, Richard J O'Reilly, Marcel R M van den Brink, Johannes L Zakrzewski
BACKGROUND: Even though hematopoietic stem cell transplantation can be curative in patients with severe combined immunodeficiency, there is a need for additional strategies boosting T cell immunity in individuals suffering from genetic disorders of lymphoid development. Here we show that image-guided intrathymic injection of hematopoietic stem and progenitor cells in NOD-scid IL2rγ(null) mice is feasible and facilitates the generation of functional T cells conferring protective immunity...
May 16, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28507865/reconstitution-of-human-keloids-in-mouse-skin
#3
Ataru Sunaga, Hideaki Kamochi, Shunji Sarukawa, Hirokazu Uda, Yasushi Sugawara, Rintaro Asahi, Daekwan Chi, Shiho Nakagawa, Koji Kanayama, Kotaro Yoshimura
BACKGROUND: Keloids are a dermal fibroproliferative scar of unknown etiology. There is no good animal model for the study of keloids, which hinders the development and assessment of treatments for keloids. METHODS: Human keratinocytes and dermal fibroblasts were isolated from 3 human skin tissues: normal skin, white scars, and keloids. A mixed-cell slurry containing keratinocytes and dermal fibroblasts was poured into a double chamber implanted on the back of NOD/Shi-scid/IL-2Rγnull mice...
April 2017: Plastic and Reconstructive Surgery. Global Open
https://www.readbyqxmd.com/read/28507809/t-cell-therapy-targeting-a-public-neoantigen-in-microsatellite-instable-colon-cancer-reduces-in-vivo-tumor-growth
#4
Else M Inderberg, Sébastien Wälchli, Marit R Myhre, Sissel Trachsel, Hilde Almåsbak, Gunnar Kvalheim, Gustav Gaudernack
T-cell receptor (TCR) transfer is an attractive strategy to increase the number of cancer-specific T cells in adoptive cell therapy. However, recent clinical and pre-clinical findings indicate that careful consideration of the target antigen is required to limit the risk of off-target toxicity. Directing T cells against mutated proteins such as frequently occurring frameshift mutations may thus be a safer alternative to tumor-associated self-antigens. Furthermore, such frameshift mutations result in novel polypeptides allowing selection of TCRs from the non-tolerant T-cell repertoire circumventing the problem of low affinity TCRs due to central tolerance...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28500395/the-human-serum-protein-c4b-binding-protein-inhibits-pancreatic-iapp-induced-inflammasome-activation
#5
Klaudia Kulak, Gunilla T Westermark, Nikolina Papac-Milicevic, Erik Renström, Anna M Blom, Ben C King
AIMS/HYPOTHESIS: Inflammasome activation and subsequent IL-1β production is a driver of islet pathology in type 2 diabetes. Oligomers, but not mature amyloid fibrils, of human islet amyloid polypeptide (IAPP), which is co-secreted with insulin, trigger NOD-like receptor pyrin domain containing-3 (NLRP3) inflammasome activation. C4b-binding protein (C4BP), present in serum, binds to IAPP and affects transition of IAPP monomers and oligomers to amyloid fibrils. We therefore hypothesised that C4BP inhibits IAPP-mediated inflammasome activation and IL-1β production...
May 12, 2017: Diabetologia
https://www.readbyqxmd.com/read/28499273/inhibition-of-nlrp3-inflammasome-by-thioredoxin-interacting-protein-in-mouse-kupffer-cells-as-a-regulatory-mechanism-for-non-alcoholic-fatty-liver-disease-development
#6
Kun He, Xiwen Zhu, Yan Liu, Chunmu Miao, Tao Wang, Peizhi Li, Lei Zhao, Yaxi Chen, Junhua Gong, Can Cai, Jinzheng Li, Shengwei Li, Xiong Z Ruan, Jianping Gong
NOD-like receptor (NLR) NLRP3 inflammasome activation has been implicated in the progression of non-alcoholic fatty liver disease (NAFLD) from non-alcoholic fatty liver (NAFL) to non-alcoholic steatohepatitis (NASH). It has been also shown that palmitic acid (PA) activates NLRP3 inflammasome and promotes interleukin-1β (IL-1β) secretion in Kupffer cells (KCs). However, the specific mechanism of the NLRP3 inflammasome activation is unclear. We studies the molecular mechanisms by investigating the roles of Thioredoxin-interacting protein (TXNIP) and NLRP3 on NAFLD development in patients, high-fat diet (HFD)-induced NAFL and methionine choline deficient (MCD) diet-induced NASH in wild type (WT), TXNIP-/- (thioredoxin-interacting protein) and NLRP3-/- mice, and isolated KCs...
April 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28497484/cd44-variant-isoform-9-emerges-in-response-to-injury-and-contributes-to-the-regeneration-of-the-gastric-epithelium
#7
Nina Bertaux-Skeirik, Mark Wunderlich, Emma Teal, Jayati Chakrabarti, Jacek Biesiada, Maxime Mahe, Nambirajan Sundaram, Joel Gabre, Jennifer Hawkins, Jian Gao, Amy C Engevik, Li Yang, Jiang Wang, James R Goldenring, Joseph E Qualls, Mario Medvedovic, Michael A Helmrath, Tayyab Diwan, James C Mulloy, Yana Zavros
Cluster-of-differentiation gene 44, in particular CD44 variant isoform 9 (CD44v9), emerges during regeneration of the gastric epithelium in response to injury. In particular, CD44v9 is expressed within Spasmolytic Polypeptide/TFF2-Expressing Metaplasia (SPEM) glands during gastric repair, but the function is unknown. Here we tested the hypothesis that age dependent expression of CD44v9 marks a regenerative cell lineage responsive to infiltrating macrophages during regeneration of the gastric epithelium. Acetic acid injury was induced in CD44-deficient (CD44KO) and C57BL/6 (BL6) mice...
May 12, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/28489059/the-impact-of-diet-wheat-source-on-the-onset-of-type-1-diabetes-mellitus-lessons-learned-from-the-non-obese-diabetic-nod-mouse-model
#8
Jonathan Gorelick, Ludmila Yarmolinsky, Arie Budovsky, Boris Khalfin, Joshua D Klein, Yosi Pinchasov, Maxim A Bushuev, Tatiana Rudchenko, Shimon Ben-Shabat
Nutrition, especially wheat consumption, is a major factor involved in the onset of type 1 diabetes (T1D) and other autoimmune diseases such as celiac. While modern wheat cultivars possess similar gliadin proteins associated with the onset of celiac disease and T1D, alternative dietary wheat sources from Israeli landraces and native ancestral species may be lacking the epitopes linked with T1D, potentially reducing the incidence of T1D. The Non-Obese Diabetic (NOD) mouse model was used to monitor the effects of dietary wheat sources on the onset and development of T1D...
May 10, 2017: Nutrients
https://www.readbyqxmd.com/read/28465508/cd8-t-cells-contribute-to-lacrimal-gland-pathology-in-the-nonobese-diabetic-mouse-model-of-sj%C3%A3-gren-syndrome
#9
Jennifer Y Barr, Xiaofang Wang, David K Meyerholz, Scott M Lieberman
Sjögren syndrome is an autoimmune disease characterized by targeted destruction of the lacrimal and salivary glands resulting in symptoms of severe ocular and oral dryness. Despite its prevalence, the mechanisms driving autoimmune manifestations are unclear. In patients and in the nonobese diabetic (NOD) mouse model of Sjögren syndrome, lymphocytic infiltrates consist of CD4 and CD8 T cells, although the role of CD8 T cells in disease pathogenesis has been largely unexplored. Here, we evaluated the contribution of CD8 T cells to lacrimal and salivary gland autoimmunity...
May 3, 2017: Immunology and Cell Biology
https://www.readbyqxmd.com/read/28461573/genetic-and-small-molecule-disruption-of-the-aid-rad51-axis-similarly-protects-nonobese-diabetic-mice-from-type-1-diabetes-through-expansion-of-regulatory-b-lymphocytes
#10
Jeremy J Ratiu, Jeremy J Racine, Muneer G Hasham, Qiming Wang, Jane A Branca, Harold D Chapman, Jing Zhu, Nina Donghia, Vivek Philip, William H Schott, Clive Wasserfall, Mark A Atkinson, Kevin D Mills, Caroline M Leeth, David V Serreze
B lymphocytes play a key role in type 1 diabetes (T1D) development by serving as a subset of APCs preferentially supporting the expansion of autoreactive pathogenic T cells. As a result of their pathogenic importance, B lymphocyte-targeted therapies have received considerable interest as potential T1D interventions. Unfortunately, the B lymphocyte-directed T1D interventions tested to date failed to halt β cell demise. IgG autoantibodies marking humans at future risk for T1D indicate that B lymphocytes producing them have undergone the affinity-maturation processes of class switch recombination and, possibly, somatic hypermutation...
May 1, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28456746/genetically-engineered-mesenchymal-stromal-cells-producing-il3-and-tpo-to-further-improve-human-scaffold-based-xenograft-models
#11
M Carretta, B de Boer, J Jaques, A Antonelli, S J Horton, H Yuan, J D de Bruijn, R W J Groen, E Vellenga, J J Schuringa
Recently, NOD-SCID IL2Rγ(-/-) (NSG) mice were implanted with human mesenchymal stromal cells (MSCs) in the presence of ceramic scaffolds or matrigel in order to mimic the human bone marrow (BM) microenvironment. This approach allowed the engraftment of leukemic samples that failed to engraft in NSG mice without humanized niches and resulted in a better preservation of leukemic stem cell self-renewal properties [1-3]. To further improve our humanized niche scaffold model, we genetically engineered human MSCs to secrete human IL3 and TPO...
April 26, 2017: Experimental Hematology
https://www.readbyqxmd.com/read/28456018/unique-features-in-the-presentation-of-insulin-epitopes-in-autoimmune-diabetes-an-update
#12
REVIEW
Xiaoxiao Wan, Emil R Unanue
Although an autoimmune disease involves diverse self-antigens, the initiation stage may require recognition of a limited number. This concept is verified in the non-obese diabetic (NOD) mouse model of autoimmune diabetes, in which strong evidence points to insulin as the prime antigen. The NOD mouse bears the I-A(g7) class II-MHC molecules (MHCII) that share common biochemical features and peptidome selection with the human diabetes-susceptible HLA-DQ8. Furthermore, both NOD mice and patients with type 1 diabetes (T1D) display an early appearance of insulin autoantibodies (IAAs) and subsequent insulin-reactive T cell infiltration into the islets...
April 26, 2017: Current Opinion in Immunology
https://www.readbyqxmd.com/read/28455654/metabolically-inactive-insulin-analogue-does-not-prevent-autoimmune-diabetes-in-nod-mice
#13
Juha Grönholm, Philippe P Pagni, Minh N Pham, Claire B Gibson, Paul F Macomber, José Luis Vela, Matthias von Herrath, Michael J Lenardo
AIMS/HYPOTHESIS: Insulin is widely considered to be a driver antigen in type 1 diabetes in humans and in mouse models of the disease. Therefore, insulin or insulin analogues are candidates for tolerogenic drugs to prevent disease onset in individuals with risk of diabetes. Previous experiments have shown that autoimmune diabetes can be prevented in NOD mice by repeated doses of insulin administered via an oral, nasal or parenteral route, but clinical trials in humans have not succeeded...
April 28, 2017: Diabetologia
https://www.readbyqxmd.com/read/28453414/innate-immune-gene-transcript-level-associated-with-the-infection-of-macrophages-with-ectromelia-virus-in-two-different-mouse-strains
#14
Patryk Dolega, Lidia Szulc-Dąbrowska, Magdalena Bossowska, Matylda Mielcarska, Zuzanna Nowak, Felix N Toka
Poxviruses have evolved numerous mechanisms to avoid the immune response of the infected host, and many of these mechanisms have not been fully described. Here, we studied the transcriptional response of innate immune genes in BALB/c and C57BL/6 peritoneal macrophages following infection with the Moscow strain of ectromelia virus (ECTV-Mos) with the aim of delineating innate immune genes that contribute to the difference between susceptibility and resistance to lethal infection. We show a generalized downregulation of many genes in four categories (toll-like receptor signaling, NOD-like receptor signaling, RIG-I-like receptor signaling, and type I interferon signaling) of antiviral innate immune receptors, downstream signaling pathways, and responsive components...
April 28, 2017: Viral Immunology
https://www.readbyqxmd.com/read/28449218/development-and-pharmacologic-characterization-of-the-rat-6-hz-model-of-partial-seizures
#15
Cameron S Metcalf, Peter J West, Kyle E Thomson, Sharon F Edwards, Misty D Smith, H S White, Karen S Wilcox
OBJECTIVE: The mouse 6 Hz model of psychomotor seizures is a well-established and commonly used preclinical model for antiseizure drug (ASD) discovery. Despite its widespread use both in the identification and differentiation of novel ASDs in mice, a corresponding assay in rats has not been developed. We established a method for 6 Hz seizure induction in rats, with seizure behaviors similar to those observed in mice including head nod, jaw clonus, and forelimb clonus. METHODS: A convulsive current that elicits these seizure behaviors in 97% of rats (CC97 ) was determined using a Probit analysis...
April 27, 2017: Epilepsia
https://www.readbyqxmd.com/read/28438626/near-infrared-intraoperative-molecular-imaging-can-identify-metastatic-lymph-nodes-in-prostate-cancer
#16
Leilei Xia, Ryan Zeh, Jack Mizelle, Andrew Newton, Jarrod Predina, Shuming Nie, Sunil Singhal, Thomas J Guzzo
OBJECTIVE: To propose a novel method to perform indocyanine green (ICG) based near-infrared (NIR) fluorescence imaging during pelvic lymph node dissection (PLND) for prostate cancer patients with lymph node metastasis (LNM). MATERIALS AND METHODS: A prostate cancer cell line PC3 was used to establish xenograft model in NOD/SCID mouse. After tumor growth, mice were injected through the tail vein with ICG. Xenografts and surrounding tissues were imaged with NIR camera 24 hours after intravenous ICG and tumor-to-background ratios (TBRs) were calculated...
April 21, 2017: Urology
https://www.readbyqxmd.com/read/28424681/the-spontaneous-autoimmune-neuromyopathy-in-icosl-nod-mice-is-cd4-t-cell-and-interferon-%C3%AE-dependent
#17
Claire Briet, Gwladys Bourdenet, Ute C Rogner, Chantal Becourt, Isabelle Tardivel, Laurent Drouot, Christophe Arnoult, Jean-Claude do Rego, Nicolas Prevot, Charbel Massaad, Olivier Boyer, Christian Boitard
Abrogation of ICOS/ICOS ligand (ICOSL) costimulation prevents the onset of diabetes in the non-obese diabetic (NOD) mouse but, remarkably, yields to the development of a spontaneous autoimmune neuromyopathy. At the pathological level, ICOSL(-/-) NOD mice show stronger protection from insulitis than their ICOS(-/-) counterparts. Also, the ICOSL(-/-) NOD model carries a limited C57BL/6 region containing the Icosl nul mutation, but, in contrast to ICOS(-/-) NOD mice, no gene variant previously reported as associated to NOD diabetes...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28412308/genistein-prevention-of-hyperglycemia-and-improvement-of-glucose-tolerance-in-adult-non-obese-diabetic-mice-are-associated-with-alterations-of-gut-microbiome-and-immune-homeostasis
#18
Guannan Huang, Joella Xu, Daniel E Lefever, Travis C Glenn, Tamas Nagy, Tai L Guo
Although studies have linked soy phytoestrogen 4,7,4-trihydroxyisoflavone genistein (GEN) to reduced type 1 diabetes (T1D) risk, the mechanism of dietary GEN on T1D remains unknown. In our studies, adult non-obese diabetic (NOD) mouse model was employed to investigate the effects of GEN exposure on blood glucose level (BGL), glucose tolerance, gut microbiome, and immune responses. Adult male and female NOD mice were fed with either soy-based or casein-based diet, and received GEN at 20mg/kg body weight by gavage daily...
April 12, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28392419/early-phase-dynamics-of-traceable-mcherry-fluorescent-protein-carrying-hiv-1-infection-in-human-peripheral-blood-mononuclear-cells-transplanted-nod-scid-jak3-mice
#19
Nobuyo Higashi-Kuwata, Hiromi Ogata-Aoki, Shin-Ichiro Hattori, Hironori Hayashi, Matthew Danish, Manabu Aoki, Chiemi Shiotsu, Tatsuyoshi Kawamura, Hironobu Ihn, Hisataka Kobayashi, Seiji Okada, Hiroaki Mitsuya
We attempted to elucidate early-phase dynamics of HIV-1 infection using replication-competent, red-fluorescent-protein (mCherry)-labeled HIV-1JR-FL (HIVJR-FL(mC)) and NOD/SCID/Jak3(-/-) mice transplanted with Individual-A's human peripheral blood mononuclear cells (hPBMC)(hNOJ mice). On day 7 following HIVJR-FL(mC) inoculation, mCherry-signal-emitting infection foci were readily identified in the subserosa of 10 of 10 HIVJR-FL(mC)-inoculated hNOJ mice, although infection foci were not located without the mCherry signal in unlabeled HIV-1JR-FL-inoculated mice (n = 6)...
April 6, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28390927/a-novel-hemolytic-complement-sufficient-nsg-mouse-model-supports-studies-of-complement-mediated-antitumor-activity-in-vivo
#20
Mohit K Verma, Julia Clemens, Lisa Burzenski, Stephen B Sampson, Michael A Brehm, Dale L Greiner, Leonard D Shultz
Monoclonal antibodies (mAbs) have emerged as a mainstream therapeutic option against cancer. mAbs mediate tumor cell-killing through several mechanisms including complement-dependent cytotoxicity (CDC). However, studies of mAb-mediated CDC against tumor cells remain largely dependent on in vitro systems. Previously developed and widely used NOD-scid IL2rγ(null) (NSG) mice support enhanced engraftment of many primary human tumors. However, NSG mice have a 2-bp deletion in the coding region of the hemolytic complement (Hc) gene, and it is not possible to evaluate CDC activity in NSG mice...
April 6, 2017: Journal of Immunological Methods
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