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https://www.readbyqxmd.com/read/27899739/impact-of-immune-deficiency-on-remodeling-of-maternal-resistance-vasculature-4-weeks-postpartum-in-mice
#1
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
#2
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
#3
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...
October 20, 2016: Nutrition Research
https://www.readbyqxmd.com/read/27863852/the-rag-recombinase-beyond-breaking
#4
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
#5
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
#6
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...
November 11, 2016: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/27832860/adiponectin-administration-prevents-weight-gain-and-glycemic-profile-changes-in-diet-induced-obese-immune-deficient-rag1-mice-lacking-mature-lymphocytes
#7
Xiaowen Liu, Nikolaos Perakakis, Huizhi Gong, John P Chamberland, Mary T Brinkoetter, Ole-Petter R Hamnvik, Christos S Mantzoros
BACKGROUND: Obesity is associated with chronic low-grade inflammation leading to insulin resistance and diabetes. Adiponectin is an adipokine that regulates inflammatory responses. The aim of our study was to investigate whether any effects of adiponectin against obesity and insulin-resistance may depend on the adaptive immune system. METHODS: We treated high-fat-diet fed Rag1-/- mice lacking mature lymphocytes with adiponectin over 7weeks and investigated alterations in their metabolic outcome and inflammatory state...
December 2016: Metabolism: Clinical and Experimental
https://www.readbyqxmd.com/read/27825771/riches-in-rags-revealing-the-v-d-j-recombinase-through-high-resolution-structures
#8
REVIEW
Karla K Rodgers
Development of the adaptive immune system is dependent on V(D)J recombination, which forms functional antigen receptor genes through rearrangement of component gene segments. The V(D)J recombinase, comprising recombination-activating proteins RAG1 and RAG2, guides the initial DNA cleavage events to the recombination signal sequence (RSS), which flanks each gene segment. Although the enzymatic steps for RAG-mediated endonucleolytic activity were established over two decades ago, only recently have high-resolution structural studies of the catalytically active core regions of the RAG proteins shed light on conformational requirements for the reaction...
November 5, 2016: Trends in Biochemical Sciences
https://www.readbyqxmd.com/read/27825654/reprogramming-macrophage-orientation-by-microrna-146b-targeting-transcription-factor-irf5
#9
Liang Peng, Hui Zhang, Yuanyuan Hao, Feihong Xu, Jianjun Yang, Ruihua Zhang, Geming Lu, Zihan Zheng, Miao Cui, Chen-Feng Qi, Chun Chen, Juan Wang, Yuan Hu, Di Wang, Susan Pierce, Liwu Li, Huabao Xiong
The regulation of macrophage orientation pathological conditions is important but still incompletely understood. Here, we show that IL-10 and Rag1 double knockout mice spontaneously develop colitis with dominant M1 macrophage phenotype, suggesting that IL-10 regulates macrophage orientation in inflammation. We demonstrate that IL-10 stimulation induced miR-146b expression, and that the expression of miR-146b was impaired in IL-10 deficient macrophages. Our data show that miR-146b targets IRF5, resulting in the regulation of macrophage activation...
October 29, 2016: EBioMedicine
https://www.readbyqxmd.com/read/27808398/homozygous-deletion-of-rag1-rag2-and-5-region-traf6-causes-severe-immune-suppression-and-atypical-osteopetrosis
#10
Monika Weisz Hubshman, Lina Basel-Vanagaite, Aviva Krauss, Osnat Konen, Yael Levy, Ben Zion Garty, Pola Smirin-Yosef, Idit Maya, Irina Lagovsky, Ellen Taub, Daphna Marom, Dafna Gaash, Keren Shichrur, Smadar Avigad, Lucille Hayman Manzur, Anna Villa, Cristina Sobacchi, Mordechai Shohat, Isaac Yaniv, Jerry Stein
Mutations of several genes have been implicated in autosomal recessive osteopetrosis (OP), a disease caused by impaired function and differentiation of osteoclasts. Severe combined immune deficiencies (SCID) can likewise result from different genetic mutations. We report two siblings with SCID and an atypical phenotype of OP. A biallelic microdeletion encompassing the 5' region of TRAF6, RAG1 and RAG2 genes was identified. TRAF6, a tumor necrosis factor receptor-associated family member, plays an important role in T-cell signaling and in RANKL-dependent osteoclast differentiation and activation but its role in human OP has not been previously reported...
November 3, 2016: Clinical Genetics
https://www.readbyqxmd.com/read/27803171/the-early-adaptive-immune-response-in-the-pathophysiology-of-pneumococcal-meningitis
#11
Sandra Ribes, Stefan Nessler, Ev-Christin Heide, Dörthe Malzahn, Christina Perske, Wolfgang Brück, Roland Nau
BACKGROUND:  The adaptive immune system has been considered to play a minimal role in the early host response during bacterial meningitis. METHODS:  We investigated the progression and outcome of pneumococcal meningitis in Rag1(-/-) mice lacking functional B and T cells by overall and symptom-free survival, bacteriological and histological studies, as well as flow cytometry and measurements of pro-inflammatory mediators. RESULTS:  The intracerebral injection of S...
October 31, 2016: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/27799525/expression-of-hiv-1-matrix-protein-p17-and-association-with-b-cell-lymphoma-in-hiv-1-transgenic-mice
#12
Virginia A Carroll, Mark K Lafferty, Luigi Marchionni, Joseph L Bryant, Robert C Gallo, Alfredo Garzino-Demo
HIV-1 infection is associated with increased risk for B-cell lymphomas. How HIV infection promotes the development of lymphoma is unclear, but it may involve chronic B-cell activation, inflammation, and/or impaired immunity, possibly leading to a loss of control of oncogenic viruses and reduced tumor immunosurveillance. We hypothesized that HIV structural proteins may contribute to lymphomagenesis directly, because they can persist long term in lymph nodes in the absence of viral replication. The HIV-1 transgenic mouse Tg26 carries a noninfectious HIV-1 provirus lacking part of the gag-pol region, thus constituting a model for studying the effects of viral products in pathogenesis...
November 15, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27798187/cd8-t-cells-and-endogenous-il-10-are-required-for-resolution-of-chemotherapy-induced-neuropathic-pain
#13
Karen Krukowski, Niels Eijkelkamp, Geoffroy Laumet, C Erik Hack, Yan Li, Patrick M Dougherty, Cobi J Heijnen, Annemieke Kavelaars
: Chemotherapy-induced peripheral neuropathy (CIPN), characterized by pain and numbness in hands and feet, is a common side effect of cancer treatment. In most patients, symptoms of CIPN subside after treatment completion. However, in a substantial subgroup, CIPN persists long into survivorship. Impairment in pain resolution pathways may explain persistent CIPN. We investigated the contribution of T cells and endogenous interleukin (IL)-10 to resolution of CIPN. Paclitaxel-induced mechanical allodynia was prolonged in T-cell-deficient (Rag1(-/-)) mice compared with wild-type (WT) mice...
October 26, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27798153/t-cell-independent-mechanisms-associated-with-neutrophil-extracellular-trap-formation-and-selective-autophagy-in-il-17a-mediated-epidermal-hyperplasia
#14
Erika Suzuki, Emanual Maverakis, Ritu Sarin, Laura Bouchareychas, Vijay K Kuchroo, Frank O Nestle, Iannis E Adamopoulos
IL-17A has been strongly associated with epidermal hyperplasia in many cutaneous disorders. However, because IL-17A is mainly produced by αβ and γδT cells in response to IL-23, the role of T cells and IL-23 has overshadowed any IL-17A-independent actions. In this article, we report that IL-17A gene transfer induces epidermal hyperplasia in Il23r(-/-)Rag1(-/-)- and Tcrδ-deficient mice, which can be prevented by neutrophil depletion. Moreover, adoptive transfer of CD11b(+)Gr-1(hi) cells, after IL-17A gene transfer, was sufficient to phenocopy the disease...
December 1, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27702897/real-time-analysis-of-rag-complex-activity-in-v-d-j-recombination
#15
Jennifer Zagelbaum, Noriko Shimazaki, Zitadel Anne Esguerra, Go Watanabe, Michael R Lieber, Eli Rothenberg
Single-molecule FRET (smFRET) and single-molecule colocalization (smCL) assays have allowed us to observe the recombination-activating gene (RAG) complex reaction mechanism in real time. Our smFRET data have revealed distinct bending modes at recombination signal sequence (RSS)-conserved regions before nicking and synapsis. We show that high mobility group box 1 (HMGB1) acts as a cofactor in stabilizing conformational changes at the 12RSS heptamer and increasing RAG1/2 binding affinity for 23RSS. Using smCL analysis, we have quantitatively measured RAG1/2 dwell time on 12RSS, 23RSS, and non-RSS DNA, confirming a strict RSS molecular specificity that was enhanced in the presence of a partner RSS in solution...
October 18, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27701347/phylogeny-and-genetic-variation-within-the-widely-distributed-bluntnose-minnow-pimephales-notatus-cyprinidae-in-north-america
#16
Susana Schönhuth, Collin E Beachum, Jason H Knouft, Richard L Mayden
This study represents a phylogenetic analysis of Pimephales notatus, a widely distributed North American cyprinid fish species, using one mitochondrial (cytb) and two nuclear (S7 and Rag1) genes. Despite the broad geographic distribution of this species that includes independent basins, results suggest a largely drainage-independent genetic structure. Results reveal a well-supported lineage in the Ozark Highlands, which is highly divergent from the remaining populations and may represent a long-term isolated lineage that should be considered as a separate conservation and management unit...
September 14, 2016: Zootaxa
https://www.readbyqxmd.com/read/27693323/interleukin-1%C3%AE-mediates-intestinal-inflammation-in-mice-and-patients-with-interleukin-10-receptor-deficiency
#17
Dror S Shouval, Amlan Biswas, Yu Hui Kang, Alexandra E Griffith, Liza Konnikova, Ivan D Mascanfroni, Naresh S Redhu, Sandra M Frei, Michael Field, Andria L Doty, Jeffrey D Goldsmith, Atul K Bhan, Anthony Loizides, Batia Weiss, Baruch Yerushalmi, Tadahiro Yanagi, Xiuli Lui, Francisco J Quintana, Aleixo M Muise, Christoph Klein, Bruce H Horwitz, Sarah C Glover, Athos Bousvaros, Scott B Snapper
Interleukin 10 receptor (IL10R)-deficient mice develop spontaneous colitis and, similarly, patients with loss-of-function mutations in IL10R develop severe infant-onset inflammatory bowel disease. Loss of IL10R signaling in mouse and human macrophages is associated with increased production of interleukin 1β. We demonstrated that innate immune production of IL1β mediates colitis in IL10R-deficient mice. Transfer of Il1r1(-/-) CD4(+) T cells into Rag1(-/-)/Il10rb(-/-) mice reduced the severity of their colitis (compared to mice that received CD4(+) T cells that express IL1R), accompanied by decreased production of interferon gamma, tumor necrosis factor-α, and IL17A...
December 2016: Gastroenterology
https://www.readbyqxmd.com/read/27664344/leapfrogging-into-new-territory-how-mascarene-ridged-frogs-diversified-across-africa-and-madagascar-to-maintain-their-ecological-niche
#18
Breda M Zimkus, Lucinda P Lawson, Michael Barej, Christopher D Barratt, Alan Channing, Katrina M Dash, J Maximilian Dehling, Louis Du Preez, Philip-Sebastian Gehring, Eli Greenbaum, Václav Gvoždík, James Harvey, Jos Kielgast, Chifundera Kusamba, Zoltán T Nagy, Maciej Pabijan, Johannes Penner, Mark-Oliver Rödel, Miguel Vences, Stefan Lötters
The Mascarene ridged frog, Ptychadena mascareniensis, is a species complex that includes numerous lineages occurring mostly in humid savannas and open forests of mainland Africa, Madagascar, the Seychelles, and the Mascarene Islands. Sampling across this broad distribution presents an opportunity to examine the genetic differentiation within this complex and to investigate how the evolution of bioclimatic niches may have shaped current biogeographic patterns. Using model-based phylogenetic methods and molecular-clock dating, we constructed a time-calibrated molecular phylogenetic hypothesis for the group based on mitochondrial 16S rRNA and cytochrome b (cytb) genes and the nuclear RAG1 gene from 173 individuals...
September 21, 2016: Molecular Phylogenetics and Evolution
https://www.readbyqxmd.com/read/27643385/ror%C3%AE-t-antagonist-suppresses-m3-muscarinic-acetylcholine-receptor-induced-sj%C3%A3-gren-s-syndrome-like-sialadenitis
#19
M Tahara, H Tsuboi, S Segawa, H Asashima, M Iizuka-Koga, T Hirota, H Takahashi, Y Kondo, M Matsui, I Matsumoto, T Sumida
We showed recently that M3 muscarinic acetylcholine receptor (M3R)-reactive CD3(+) T cells play a pathogenic role in the development of murine autoimmune sialadenitis (MIS), which mimics Sjögren's syndrome (SS). The aim of this study was to determine the effectiveness and mechanism of action of retinoic acid-related orphan receptor-gamma t (RORγt) antagonist (A213) in MIS. Splenocytes from M3R knockout (M3R(-/-) ) mice immunized with murine M3R peptide mixture were inoculated into recombination-activating gene 1 knockout (Rag-1(-/-) ) mice (M3R(-/-) →Rag-1(-/-) ) with MIS...
September 19, 2016: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/27621418/rag-induced-dna-lesions-activate-proapoptotic-bim-to-suppress-lymphomagenesis-in-p53-deficient-mice
#20
Alex R D Delbridge, Swee Heng Milon Pang, Cassandra J Vandenberg, Stephanie Grabow, Brandon J Aubrey, Lin Tai, Marco J Herold, Andreas Strasser
Neoplastic transformation is driven by oncogenic lesions that facilitate unrestrained cell expansion and resistance to antiproliferative signals. These oncogenic DNA lesions, acquired through errors in DNA replication, gene recombination, or extrinsically imposed damage, are thought to activate multiple tumor suppressive pathways, particularly apoptotic cell death. DNA damage induces apoptosis through well-described p53-mediated induction of PUMA and NOXA. However, loss of both these mediators (even together with defects in p53-mediated induction of cell cycle arrest and cell senescence) does not recapitulate the tumor susceptibility observed in p53(-/-) mice...
September 19, 2016: Journal of Experimental Medicine
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