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https://www.readbyqxmd.com/read/28087429/analysis-of-parameters-that-affect-human-hematopoietic-cell-outputs-in-mutant-c-kit-immunodeficient-mice
#1
Paul H Miller, Gabrielle Rabu, Margarita MacAldaz, David Jhf Knapp, Alice Ms Cheung, Kiran Dhillon, Naoto Nakamichi, Philip A Beer, Leonard D Shultz, R Keith Humphries, Connie J Eaves
Xenograft models are transforming our understanding of the output capabilities of primitive human hematopoietic cells in vivo. However, many variables that affect post-transplant reconstitution dynamics remain poorly understood. Here we show an equivalent level of human chimerism can be regenerated from human CD34(+) cord blood cells transplanted intravenously either with or without additional radiation-inactivated cells into 2-6 month-old NOD-Rag1(-/-)-IL2Rγc(-/-) (NRG) mice given a more radioprotective conditioning regimen than is possible in conventionally used, repair-deficient, NOD-Prkdc(scid/scid)-IL2Rγc(-/-) (NSG) hosts...
January 10, 2017: Experimental Hematology
https://www.readbyqxmd.com/read/28077655/expression-of-ifnlr1-on-intestinal-epithelial-cells-is-critical-to-the-antiviral-effects-of-ifn-lambda-against-norovirus-and-reovirus
#2
Megan T Baldridge, Sanghyun Lee, Judy J Brown, Nicole McAllister, Kelly Urbanek, Terence S Dermody, Timothy J Nice, Herbert W Virgin
: Interferon-lambda (IFN-λ) has potent antiviral effects against multiple enteric viral pathogens, including norovirus and rotavirus, in both preventing and curing infection. Because the intestine includes a diverse array of cell types, however, the cell(s) upon which IFN-λ acts to exert its antiviral effects are unclear. Here, we sought to identify IFN-λ responsive cells by generation of mice with lineage-specific deletion of the receptor for IFN-λ, Ifnlr1 We found that expression of IFNLR1 on intestinal epithelial cells (IECs) in the small intestine and colon is required for enteric IFN-λ antiviral activity...
January 11, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28058717/deletional-tolerance-prevents-aqp4-directed-autoimmunity-in-mice
#3
Anna-Lena Vogel, Benjamin Knier, Katja Lammens, Sudhakar Reddy Kalluri, Tanja Kuhlmann, Jeffrey L Bennett, Thomas Korn
Neuromyelitis optica (NMO) is an autoimmune disorder of the central nervous system (CNS) mediated by antibodies to water channel protein AQP4 expressed in astrocytes. The contribution of AQP4-specific T cells to the class switch recombination of pathogenic AQP4-specific antibodies and to the inflammation of the blood-brain-barrier is incompletely understood, as immunogenic naturally processed T-cell epitopes of AQP4 are unknown. By immunizing Aqp4(-/-) mice with full length murine AQP4 protein followed by recall with overlapping peptides, we here identify AQP4(201-220) as the major immunogenic IA(b) -restricted epitope of AQP4...
January 5, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28049044/lymphocytes-contribute-to-biliary-injury-and-fibrosis-in-experimental-xenobiotic-induced-cholestasis
#4
Nikita Joshi, Anna K Kopec, Holly Cline-Fedewa, James P Luyendyk
The etiology of chronic bile duct injury and fibrosis in patients with autoimmune cholestatic liver diseases is complex, and likely involves immune cells such as lymphocytes. However, most models of biliary fibrosis are not autoimmune in nature. Biliary fibrosis can be induced experimentally by prolonged exposure of mice to the bile duct toxicant alpha-naphthylisothiocyanate (ANIT). We determined whether lymphocytes contributed to ANIT-mediated biliary hyperplasia and fibrosis in mice. Hepatic accumulation of T-lymphocytes and increased serum levels of anti-nuclear-autoantibodies were evident in wild-type mice exposed to ANIT (0...
December 31, 2016: Toxicology
https://www.readbyqxmd.com/read/28039309/tissue-nonspecific-alkaline-phosphatase-expression-is-needed-for-the-full-stimulation-of-t-cells-and-t-cell-dependent-colitis
#5
Cristina Hernández-Chirlaque, Reyes Gámez-Belmonte, Borja Ocón, Patricia Martínez-Moya, Stefan Wirtz, Fermín Sánchez de Medina, Olga Martínez-Augustin
BACKGROUND AND AIMS: Two alkaline phosphatase isoforms, intestinal (IAP) and tissue non-specific alkaline phosphatase (TNAP), are coexpressed in mouse colon, with the latter predominating in colitis. We aimed to examine the role of TNAP in T lymphocytes using heterozygous TNAP(+/-) mice (as TNAP(-/-) mice are nonviable). METHODS: In vitro primary cultures and in vivo T cell models using TNAP(+/-) mice were used. RESULTS: Stimulated splenocytes (lipopolysaccharide and concanavalin A) and T lymphocytes (concanavalin A and a-CD3/a-CD28) showed a decreased cytokine production and expression when compared with WT cells...
December 30, 2016: Journal of Crohn's & Colitis
https://www.readbyqxmd.com/read/28034915/early-life-antibiotic-treatment-enhances-the-pathogenicity-of-cd4-t-cells-during-intestinal-inflammation
#6
Sebastian Scheer, Tiago S Medina, Alex Murison, Matthew D Taves, Frann Antignano, Alistair Chenery, Kiran K Soma, Georgia Perona-Wright, Mathieu Lupien, Cheryl H Arrowsmith, Daniel D De Carvalho, Colby Zaph
The incidence of inflammatory bowel diseases (IBDs) has steadily increased in recent decades-a phenomenon that cannot be explained by genetic mutations alone. Other factors, including the composition of the intestinal microbiome, are potentially important contributors to the increased occurrence of this group of diseases. Previous reports have shown a correlation between early-life antibiotic (Abx) treatment and an increased incidence of IBD. In this report, we investigated the effects of early-life Abx treatments on the pathogenicity of CD4(+) T cells using an experimental T cell transfer model of IBD...
December 29, 2016: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28031334/respiratory-influenza-virus-infection-induces-memory-like-liver-nk-cells-in-mice
#7
Tingting Li, Jian Wang, Yanshi Wang, Yongyan Chen, Haiming Wei, Rui Sun, Zhigang Tian
Although NK cells are classified as innate immune cells, recent studies have demonstrated the transformation of NK cells into long-lived memory cells that contribute to secondary immune responses in certain mouse models. However, whether NK cells mount an Ag-specific memory response to acute influenza virus infection has not yet been examined. Here, we show that, consistent with previous studies, lung NK cells play an important role in controlling viral proliferation after primary influenza virus infection...
December 28, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28025225/the-effect-of-temperature-and-host-plant-resistance-on-population-growth-of-the-soybean-aphid-biotype-1-hemiptera-aphididae
#8
Ashley R Hough, James R Nechols, Brian P McCornack, David C Margolies, Brett K Sandercock, Donglin Yan, Leigh Murray
A laboratory experiment was conducted to evaluate direct and indirect effects of temperature on demographic traits and population growth of biotype 1 of the soybean aphid, Aphis glycines Matsumura. Our objectives were to better understand how temperature influences the expression of host plant resistance, quantify the individual and interactive effects of plant resistance and temperature on soybean aphid population growth, and generate thermal constants for predicting temperature-dependent development on both susceptible and resistant soybeans...
December 26, 2016: Environmental Entomology
https://www.readbyqxmd.com/read/28017833/protein-palmitoylation-by-zdhhc13-protects-skin-against-microbial-driven-dermatitis
#9
Li-Ying Chen, Hsin-Fang Yang-Yen, Chun-Chou Tsai, Christina Li-Ping Thio, Hsiao-Li Chuang, Liang-Tung Yang, Li-Fen Shen, I-Wen Song, Kai-Ming Liu, Yen-Te Huang, Fu-Tong Liu, Ya-Jen Chang, Yuan-Tsong Chen, Jeffrey J Y Yen
Atopic dermatitis (AD) is a complex chronic inflammatory skin disorder that results from intimate interactions between genetic predisposition, host environment, skin barrier defects, and immunological factors. However, a clear genetic roadmap leading to AD remains to be fully explored. From a genome-wide mutagenesis screen, deficiency of ZDHHC13, a palmitoylacyl transferase, has previously been associated with skin and multi-tissue inflammatory phenotypes. Here, we report that ZDHHC13 is required for skin barrier integrity and that deficiency of ZDHHC13 renders mice susceptible to environmental bacteria, resulting in persistent skin inflammation and an AD-like disease...
December 22, 2016: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/28006671/recapitulation-of-treatment-response-patterns-in-a-novel-humanized-mouse-model-for-chronic-hepatitis-b-virus-infection
#10
Benjamin Y Winer, Tiffany Huang, Benjamin E Low, Cindy Avery, Mihai-Alexandru Pais, Gabriela Hrebikova, Evelyn Siu, Luis Chiriboga, Michael V Wiles, Alexander Ploss
There are ~350 million chronic carriers of hepatitis B (HBV). While a prophylactic vaccine and drug regimens to suppress viremia are available, chronic HBV infection is rarely cured. HBV's limited host tropism leads to a scarcity of susceptible small animal models and is a hurdle to developing curative therapies. Mice that support engraftment with human hepatoctyes have traditionally been generated through crosses of murine liver injury models to immunodeficient backgrounds. Here, we describe the disruption of fumarylacetoacetate hydrolase directly in the NOD Rag1(-/-) IL2RγNULL (NRG) background using zinc finger nucleases...
December 19, 2016: Virology
https://www.readbyqxmd.com/read/27975325/studying-hbv-infection-and-therapy-in-immune-deficient-nod-rag1-il2rgammac-null-nrg-fumarylacetoacetate-hydrolase-fah-knockout-mice-transplanted-with-human-hepatocytes
#11
Feng Li, Kouki Nio, Fumihiko Yasui, Christopher M Murphy, Lishan Su
Chimeric mouse models with a humanized liver provide a unique tool to study hepatic virus diseases, including viral infection, viral pathogenesis, and antiviral therapy. Here we describe a detailed protocol for studying hepatitis B infection in NRG-derived fumarylacetoacetate hydrolase (Fah) knockout mice repopulated with human hepatocytes. The procedures include (1) maintenance and genotyping of the homozygous NRG-fah/fah mutant mice (NRG/F), (2) intrasplenic injection of human hepatocytes, (3) NTBC drug reduction cycling to improve human hepatocyte repopulation, (4) human albumin detection, and (5) HBV infection and detection...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27973733/new-insights-into-the-evolutionary-origins-of-the-rag-proteins-and-v-d-j-recombination
#12
REVIEW
Lina Marcela Carmona, David G Schatz
The adaptive immune system of jawed vertebrates relies on V(D)J recombination as one of the main processes to generate the diverse array of receptors necessary for the recognition of a wide range of pathogens. The DNA cleavage reaction necessary for the assembly of the antigen receptor genes from an array of potential gene segments is mediated by the Recombination Activating Gene proteins RAG1 and RAG2. The RAG proteins have been proposed to originate from a transposable element (TE) as they share mechanistic and structural similarities with several families of transposases and are themselves capable of mediating transposition...
December 14, 2016: FEBS Journal
https://www.readbyqxmd.com/read/27966552/contraction-of-intestinal-effector-t-cells-by-retinoic-acid-induced-purinergic-receptor-p2x7
#13
S Hashimoto-Hill, L Friesen, M Kim, C H Kim
The intestinal environment harbors a large number of activated T cells, which are potentially inflammatory. To prevent inflammatory responses, intestinal T cells are controlled by various tolerogenic mechanisms, including T-cell apoptosis. We investigated the expression mechanism and function of the purinergic receptor P2X7 in contraction of intestinal CD4(+) effector T cells. We found that P2X7 upregulation on CD4(+) effector T cells is induced by retinoic acid through retinoic acid receptor α binding to an intragenic enhancer region of the P2rx7 gene...
December 14, 2016: Mucosal Immunology
https://www.readbyqxmd.com/read/27916375/the-role-of-the-adaptive-immune-system-in-burn-induced-heterotopic-ossification-and-mesenchymal-cell-osteogenic-differentiation
#14
Kavitha Ranganathan, Shailesh Agarwal, David Cholok, Shawn Loder, Jonathan Li, Hsiao Hsin Sung Hsieh, Stewart C Wang, Steven R Buchman, Benjamin Levi
BACKGROUND: Heterotopic ossification (HO) is the pathologic process of extraskeletal bone formation. Although the exact etiology remains unknown, inflammation appears to catalyze disease progression. The goal of this study is to determine the impact of the adaptive immune system on HO. METHODS: HO was induced in 8-wk-old control C57BL/6 and immunocompromised Rag1tm1Mom (Rag1 KO) male mice deficient in B- and T-lymphocytes via combined Achilles tenotomy and burn injury...
November 2016: Journal of Surgical Research
https://www.readbyqxmd.com/read/27899739/impact-of-immune-deficiency-on-remodeling-of-maternal-resistance-vasculature-4-weeks-postpartum-in-mice
#15
Elizabeth A Bonney, Ann Howard, Kendall Krebs, Kelly Begin, Kelsey Veilleux, Natalia I Gokina
Pregnancy manifests changes in the vascular and immune systems that persist postpartum (PP), have important implications for future pregnancies, and may modify responses to cardiovascular stress in late life. The association between immune and vascular function and the generation or progression of cardiovascular disease beg the question of whether altered immunity modifies pregnancy-induced changes in the vasculature. Our objective was to compare changes in the function and remodeling of systemic resistance vessels 4 weeks PP in normal C57BL/6 (B6), and immunodeficient mice recombinase 1-deficient/B6 (Rag1(-/-))...
November 28, 2016: Reproductive Sciences
https://www.readbyqxmd.com/read/27875529/cd4-t-cells-are-as-protective-as-cd8-t-cells-against-rickettsia-typhi-infection-by-activating-macrophage-bactericidal-activity
#16
Kristin Moderzynski, Stefanie Papp, Jessica Rauch, Liza Heine, Svenja Kuehl, Ulricke Richardt, Bernhard Fleischer, Anke Osterloh
Rickettsia typhi is an intracellular bacterium that causes endemic typhus, a febrile disease that can be fatal due to complications including pneumonia, hepatitis and meningoencephalitis, the latter being a regular outcome in T and B cell-deficient C57BL/6 RAG1-/- mice upon Rickettsia typhi infection. Here, we show that CD4+ TH1 cells that are generated in C57BL/6 mice upon R. typhi infection are as protective as cytotoxic CD8+ T cells. CD4+- as well as CD8+-deficient C57BL/6 survived the infection without showing symptoms of disease at any point in time...
November 2016: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/27866828/high-fat-western-diet-induced-obesity-contributes-to-increased-tumor-growth-in-mouse-models-of-human-colon-cancer
#17
Ann Marie O'Neill, Christine M Burrington, Erin A Gillaspie, Darin T Lynch, Melissa J Horsman, Michael W Greene
Strong epidemiologic evidence links colon cancer to obesity. The increasing worldwide incidence of colon cancer has been linked to the spread of the Western lifestyle, and in particular consumption of a high-fat Western diet. In this study, our objectives were to establish mouse models to examine the effects of high-fat Western diet-induced obesity on the growth of human colon cancer tumor xenografts, and to examine potential mechanisms driving obesity-linked human colon cancer tumor growth. We hypothesize that mice rendered insulin resistant due to consumption of a high-fat Western diet will show increased and accelerated tumor growth...
December 2016: Nutrition Research
https://www.readbyqxmd.com/read/27863852/the-rag-recombinase-beyond-breaking
#18
Chloé Lescale, Ludovic Deriano
DNA double-strand breaks (DSBs) are commonly seen as lesions that threaten genome integrity and contribute to cancer and aging processes. However, in the context of antigen receptor gene assembly, known as V(D)J recombination, DSBs are obligatory intermediates that allow the establishment of genetic diversity and adaptive immunity. V(D)J recombination is initiated when the lymphoid-restricted recombination-activating genes RAG1 and RAG2 are expressed and form a site-specific endonuclease (the RAG nuclease or RAG recombinase)...
November 15, 2016: Mechanisms of Ageing and Development
https://www.readbyqxmd.com/read/27849182/innate-immune-memory-contributes-to-host-defense-against-recurrent-skin-and-skin-structure-infections-caused-by-methicillin-resistant-staphylococcus-aureus
#19
Liana C Chan, Siyang Chaili, Scott G Filler, Lloyd S Miller, Norma V Solis, Huiyuan Wang, Colin W Johnson, Hong K Lee, Luis F Diaz, Michael R Yeaman
Staphylococcus aureus is the leading cause of skin and skin structure infections (SSSI). The high frequency of recurring SSSI due to S. aureus, including methicillin-resistant (MRSA) strains, despite high titers of specific antibody and circulating T cells, implies that traditional adaptive immunity imparts incomplete protection. We hypothesized that innate immune memory contributes to protective host defense against recurring MRSA infection. To test this hypothesis, SSSI was induced in wild-type and rag1(-/-) mice in BALB/c and C57BL/6 backgrounds...
November 14, 2016: Infection and Immunity
https://www.readbyqxmd.com/read/27836928/the-common-mouse-protozoa-tritrichomonas-muris-alters-mucosal-t-cell-homeostasis-and-colitis-susceptibility
#20
Nichole K Escalante, Paul Lemire, Mayra Cruz Tleugabulova, David Prescott, Arthur Mortha, Catherine J Streutker, Stephen E Girardin, Dana J Philpott, Thierry Mallevaey
The mammalian gastrointestinal tract hosts a diverse community of microbes including bacteria, fungi, protozoa, helminths, and viruses. Through coevolution, mammals and these microbes have developed a symbiosis that is sustained through the host's continuous sensing of microbial factors and the generation of a tolerant or pro-inflammatory response. While analyzing T cell-driven colitis in nonlittermate mouse strains, we serendipitously identified that a nongenetic transmissible factor dramatically increased disease susceptibility...
December 12, 2016: Journal of Experimental Medicine
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