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Richard a flavell

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https://www.readbyqxmd.com/read/28670480/long-term-consumption-of-caffeine-free-high-sucrose-cola-beverages-aggravates-the-pathogenesis-of-eae-in-mice
#1
Guangchao Cao, Qian Wang, Wanjun Huang, Jiyu Tong, Dewei Ye, Yan He, Zonghua Liu, Xin Tang, Hao Cheng, Qiong Wen, Dehai Li, Hau-Tak Chau, Yiming Wen, Hui Zhong, Ziyu Meng, Hui Liu, Zhenzhou Wu, Liqing Zhao, Richard A Flavell, Hongwei Zhou, Aimin Xu, Hengwen Yang, Zhinan Yin
Epidemiological data provide strong evidence of dramatically increasing incidences of many autoimmune diseases in the past few decades, mainly in western and westernized countries. Recent studies clearly revealed that 'Western diet' increases the risk of autoimmune diseases at least partially via disrupting intestinal tight junctions and altering the construction and metabolites of microbiota. However, the role of high sucrose cola beverages (HSCBs), which are one of the main sources of added sugar in the western diet, is barely known...
2017: Cell Discovery
https://www.readbyqxmd.com/read/28636595/nlrp9b-inflammasome-restricts-rotavirus-infection-in-intestinal-epithelial-cells
#2
Shu Zhu, Siyuan Ding, Penghua Wang, Zheng Wei, Wen Pan, Noah W Palm, Yi Yang, Hua Yu, Hua-Bing Li, Geng Wang, Xuqiu Lei, Marcel R de Zoete, Jun Zhao, Yunjiang Zheng, Haiwei Chen, Yujiao Zhao, Kellie A Jurado, Ningguo Feng, Liang Shan, Yuval Kluger, Jun Lu, Clara Abraham, Erol Fikrig, Harry B Greenberg, Richard A Flavell
Rotavirus, a leading cause of severe gastroenteritis and diarrhoea in young children, accounts for around 215,000 deaths annually worldwide. Rotavirus specifically infects the intestinal epithelial cells in the host small intestine and has evolved strategies to antagonize interferon and NF-κB signalling, raising the question as to whether other host factors participate in antiviral responses in intestinal mucosa. The mechanism by which enteric viruses are sensed and restricted in vivo, especially by NOD-like receptor (NLR) inflammasomes, is largely unknown...
June 29, 2017: Nature
https://www.readbyqxmd.com/read/28618267/enhancement-of-ifn%C3%AE-production-by-distinct-commensals-ameliorates-salmonella-induced-disease
#3
Sophie Thiemann, Nathiana Smit, Urmi Roy, Till Robin Lesker, Eric J C Gálvez, Julia Helmecke, Marijana Basic, Andre Bleich, Andrew L Goodman, Ulrich Kalinke, Richard A Flavell, Marc Erhardt, Till Strowig
The microbiota contributes to colonization resistance against invading pathogens by competing for metabolites, producing inhibitory substances, and priming protective immune responses. However, the specific commensal bacteria that promote host resistance and immune-mediated protection remain largely elusive. Using isogenic mouse lines with distinct microbiota profiles, we demonstrate that severity of disease induced by enteric Salmonella Typhimurium infection is strongly modulated by microbiota composition in individual lines...
June 14, 2017: Cell Host & Microbe
https://www.readbyqxmd.com/read/28614717/microbiota-normalization-reveals-that-canonical-caspase-1-activation-exacerbates-chemically-induced-intestinal-inflammation
#4
Adrian J Błażejewski, Sophie Thiemann, Alexander Schenk, Marina C Pils, Eric J C Gálvez, Urmi Roy, Ulrike Heise, Marcel R de Zoete, Richard A Flavell, Till Strowig
Inflammasomes play a central role in regulating intestinal barrier function and immunity during steady state and disease. Because the discoveries of a passenger mutation and a colitogenic microbiota in the widely used caspase-1-deficient mouse strain have cast doubt on previously identified direct functions of caspase-1, we reassessed the role of caspase-1 in the intestine. To this end, we generated Casp1(-/-) and Casp11(-/-) mice and rederived them into an enhanced barrier facility to standardize the microbiota...
June 13, 2017: Cell Reports
https://www.readbyqxmd.com/read/28606987/the-fate-and-lifespan-of-human-monocyte-subsets-in-steady-state-and-systemic-inflammation
#5
Amit A Patel, Yan Zhang, James N Fullerton, Lies Boelen, Anthony Rongvaux, Alexander A Maini, Venetia Bigley, Richard A Flavell, Derek W Gilroy, Becca Asquith, Derek Macallan, Simon Yona
In humans, the monocyte pool comprises three subsets (classical, intermediate, and nonclassical) that circulate in dynamic equilibrium. The kinetics underlying their generation, differentiation, and disappearance are critical to understanding both steady-state homeostasis and inflammatory responses. Here, using human in vivo deuterium labeling, we demonstrate that classical monocytes emerge first from marrow, after a postmitotic interval of 1.6 d, and circulate for a day. Subsequent labeling of intermediate and nonclassical monocytes is consistent with a model of sequential transition...
July 3, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28495875/macrophage-function-in-tissue-repair-and-remodeling-requires-il-4-or-il-13-with-apoptotic-cells
#6
Lidia Bosurgi, Y Grace Cao, Mar Cabeza-Cabrerizo, Andrea Tucci, Lindsey D Hughes, Yong Kong, Jason S Weinstein, Paula Licona-Limon, Edward T Schmid, Facundo Pelorosso, Nicola Gagliani, Joseph E Craft, Richard A Flavell, Sourav Ghosh, Carla V Rothlin
Tissue repair is a subset of a broad repertoire of interleukin-4 (IL-4)- and IL-13-dependent host responses during helminth infection. Here we show that IL-4 or IL-13 alone was not sufficient, but IL-4 or IL-13 together with apoptotic cells induced the tissue repair program in macrophages. Genetic ablation of sensors of apoptotic cells impaired the proliferation of tissue-resident macrophages and the induction of anti-inflammatory and tissue repair genes in the lungs after helminth infection or in the gut after induction of colitis...
June 9, 2017: Science
https://www.readbyqxmd.com/read/28467424/an-image-processing-and-analysis-tool-for-identifying-and-analysing-complex-plant-root-systems-in-3d-soil-using-non-destructive-analysis-root1
#7
Richard J Flavel, Chris N Guppy, Sheikh M R Rabbi, Iain M Young
The objective of this study was to develop a flexible and free image processing and analysis solution, based on the Public Domain ImageJ platform, for the segmentation and analysis of complex biological plant root systems in soil from x-ray tomography 3D images. Contrasting root architectures from wheat, barley and chickpea root systems were grown in soil and scanned using a high resolution micro-tomography system. A macro (Root1) was developed that reliably identified with good to high accuracy complex root systems (10% overestimation for chickpea, 1% underestimation for wheat, 8% underestimation for barley) and provided analysis of root length and angle...
2017: PloS One
https://www.readbyqxmd.com/read/28323879/mir-181b-regulates-vascular-stiffness-age-dependently-in-part-by-regulating-tgf-%C3%AE-signaling
#8
Daijiro Hori, Brittany Dunkerly-Eyring, Yohei Nomura, Debjit Biswas, Jochen Steppan, Jorge Henao-Mejia, Hideo Adachi, Lakshmi Santhanam, Dan E Berkowitz, Charles Steenbergen, Richard A Flavell, Samarjit Das
BACKGROUND: Endothelial dysfunction and arterial stiffening play major roles in cardiovascular diseases. The critical role for the miR-181 family in vascular inflammation has been documented. Here we tested whether the miR-181 family can influence the pathogenesis of hypertension and vascular stiffening. METHODS AND RESULTS: qPCR data showed a significant decrease in miR-181b expression in the aorta of the older mice. Eight miR-181a1/b1-/- mice and wild types (C57BL6J:WT) were followed weekly for pulse wave velocity (PWV) and blood pressure measurements...
2017: PloS One
https://www.readbyqxmd.com/read/28261564/legionella-pneumophila-strain-130b-evades-macrophage-cell-death-independent-of-the-effector-sidf-in-the-absence-of-flagellin
#9
Mary Speir, Adam Vogrin, Azadeh Seidi, Gilu Abraham, Stéphane Hunot, Qingqing Han, Gerald W Dorn, Seth L Masters, Richard A Flavell, James E Vince, Thomas Naderer
The human pathogen Legionella pneumophila must evade host cell death signaling to enable replication in lung macrophages and to cause disease. After bacterial growth, however, L. pneumophila is thought to induce apoptosis during egress from macrophages. The bacterial effector protein, SidF, has been shown to control host cell survival and death by inhibiting pro-apoptotic BNIP3 and BCL-RAMBO signaling. Using live-cell imaging to follow the L. pneumophila-macrophage interaction, we now demonstrate that L. pneumophila evades host cell apoptosis independent of SidF...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/28242633/divergent-effects-of-mir-181-family-members-on-myocardial-function-through-protective-cytosolic-and-detrimental-mitochondrial-microrna-targets
#10
Samarjit Das, Mark Kohr, Brittany Dunkerly-Eyring, Dong I Lee, Djahida Bedja, Oliver A Kent, Anthony K L Leung, Jorge Henao-Mejia, Richard A Flavell, Charles Steenbergen
BACKGROUND: MicroRNA (miRNA) is a type of noncoding RNA that can repress the expression of target genes through posttranscriptional regulation. In addition to numerous physiologic roles for miRNAs, they play an important role in pathophysiologic processes affecting cardiovascular health. Previously, we reported that nuclear encoded microRNA (miR-181c) is present in heart mitochondria, and importantly, its overexpression affects mitochondrial function by regulating mitochondrial gene expression...
February 27, 2017: Journal of the American Heart Association
https://www.readbyqxmd.com/read/28195328/visualization-of-xylem-embolism-by-x-ray-microtomography-a-direct-test-against-hydraulic-measurements
#11
Markus Nolf, Rosana Lopez, Jennifer M R Peters, Richard J Flavel, Leah S Koloadin, Iain M Young, Brendan Choat
X-ray microtomography (microCT) is becoming a valuable noninvasive tool for advancing our understanding of plant-water relations. Laboratory-based microCT systems are becoming more affordable and provide better access than synchrotron facilities. However, some systems come at the cost of comparably lower signal quality and spatial resolution than synchrotron facilities. In this study, we evaluated laboratory-based X-ray microCT imaging as a tool to nondestructively analyse hydraulic vulnerability to drought-induced embolism in a woody plant species...
February 14, 2017: New Phytologist
https://www.readbyqxmd.com/read/28167932/a-new-approach-to-modify-plant-microbiomes-and-traits-by-introducing-beneficial-bacteria-at-flowering-into-progeny-seeds
#12
Birgit Mitter, Nikolaus Pfaffenbichler, Richard Flavell, Stéphane Compant, Livio Antonielli, Alexandra Petric, Teresa Berninger, Muhammad Naveed, Raheleh Sheibani-Tezerji, Geoffrey von Maltzahn, Angela Sessitsch
The microbial component of healthy seeds - the seed microbiome - appears to be inherited between plant generations and can dynamically influence germination, plant performance, and survival. As such, methods to optimize the seed microbiomes of major crops could have far-reaching implications for plant breeding and crop improvement to enhance agricultural food, feed, and fiber production. Here, we describe a new approach to modulate seed microbiomes of elite crop seed embryos and concomitantly design the traits to be mediated by seed microbiomes...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28143932/dissection-of-neuronal-gap-junction-circuits-that-regulate-social-behavior-in-caenorhabditis-elegans
#13
Heeun Jang, Sagi Levy, Steven W Flavell, Fanny Mende, Richard Latham, Manuel Zimmer, Cornelia I Bargmann
A hub-and-spoke circuit of neurons connected by gap junctions controls aggregation behavior and related behavioral responses to oxygen, pheromones, and food in Caenorhabditis elegans The molecular composition of the gap junctions connecting RMG hub neurons with sensory spoke neurons is unknown. We show here that the innexin gene unc-9 is required in RMG hub neurons to drive aggregation and related behaviors, indicating that UNC-9-containing gap junctions mediate RMG signaling. To dissect the circuit in detail, we developed methods to inhibit unc-9-based gap junctions with dominant-negative unc-1 transgenes...
February 14, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28129537/the-stromal-intervention-regulation-of-immunity-and-inflammation-at-the-epithelial-mesenchymal-barrier
#14
REVIEW
Roni Nowarski, Ruaidhrí Jackson, Richard A Flavell
The immune system safeguards organ integrity by employing a balancing act of inflammatory and immunosuppressive mechanisms designed to neutralize foreign invaders and resolve injury. Maintaining or restoring a state of immune homeostasis is particularly challenging at barrier sites where constant exposure to immunogenic environmental agents may induce destructive inflammation. Recent studies underscore the role of epithelial and mesenchymal barrier cells in regulating immune cell function and local homeostatic and inflammatory responses...
January 26, 2017: Cell
https://www.readbyqxmd.com/read/28077418/a-novel-humanized-mouse-model-with-significant-improvement-of-class-switched-antigen-specific-antibody-production
#15
Hua Yu, Chiara Borsotti, Jean-Nicolas Schickel, Shu Zhu, Till Strowig, Elizabeth E Eynon, Davor Frleta, Cagan Gurer, Andrew J Murphy, George D Yancopoulos, Eric Meffre, Markus G Manz, Richard A Flavell
Humanized mice are a powerful tool for the study of human hematopoiesis and immune function in vivo. However, the existing models cannot support robust adaptive immune responses, especially the generation of class-switched, antigen-specific antibody responses. Here we describe a new mouse strain, in which human interleukin 6 (IL-6) gene encoding the cytokine that is important for B- and T-cell differentiation was knocked into its respective mouse locus. The provision of human IL-6 not only enhanced thymopoiesis and periphery T-cell engraftment, but also significantly increased class switched memory B cells and serum immunoglobulin G (IgG)...
February 23, 2017: Blood
https://www.readbyqxmd.com/read/28003377/il-10-receptor-signaling-is-essential-for-tr1-cell-function-in-vivo
#16
Leonie Brockmann, Nicola Gagliani, Babett Steglich, Anastasios D Giannou, Jan Kempski, Penelope Pelczar, Maria Geffken, Bechara Mfarrej, Francis Huber, Johannes Herkel, Yisong Y Wan, Enric Esplugues, Manuela Battaglia, Christian F Krebs, Richard A Flavell, Samuel Huber
IL-10 is essential to maintain intestinal homeostasis. CD4(+) T regulatory type 1 (TR1) cells produce large amounts of this cytokine and are therefore currently being examined in clinical trials as T cell therapy in patients with inflammatory bowel disease. However, factors and molecular signals sustaining TR1 cell regulatory activity still need to be identified to optimize the efficiency and ensure the safety of these trials. We investigated the role of IL-10 signaling in mature TR1 cells in vivo. Double IL-10(eGFP) Foxp3(mRFP) reporter mice and transgenic mice with impairment in IL-10 receptor signaling were used to test the activity of TR1 cells in a murine inflammatory bowel disease model, a model that resembles the trials performed in humans...
February 1, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27917411/ptpn22-inhibition-resets-defective-human-central-b-cell-tolerance
#17
Jean-Nicolas Schickel, Marcel Kuhny, Alessia Baldo, Jason M Bannock, Christopher Massad, Haowei Wang, Nathan Katz, Tyler Oe, Laurence Menard, Pauline Soulas-Sprauel, Till Strowig, Richard Flavell, Eric Meffre
The 1858T protein tyrosine phosphatase nonreceptor type 22 (PTPN22 T) allele is one of the main risk factors associated with many autoimmune diseases and correlates with a defective removal of developing autoreactive B cells in humans. To determine whether inhibiting PTPN22 favors the elimination of autoreactive B cells, we first demonstrated that the PTPN22 T allele interfered with the establishment of central B cell tolerance using NOD-scid-common γ chain knockout (NSG) mice engrafted with human hematopoietic stem cells expressing this allele...
2016: Science Immunology
https://www.readbyqxmd.com/read/27913094/hematopoietic-stem-cell-niches-produce-lineage-instructive-signals-to-control-multipotent-progenitor-differentiation
#18
Ana Cordeiro Gomes, Takahiro Hara, Vivian Y Lim, Dietmar Herndler-Brandstetter, Erin Nevius, Tatsuki Sugiyama, Shizue Tani-Ichi, Susan Schlenner, Ellen Richie, Hans-Reimer Rodewald, Richard A Flavell, Takashi Nagasawa, Koichi Ikuta, João Pedro Pereira
Hematopoietic stem cells (HSCs) self-renew in bone marrow niches formed by mesenchymal progenitors and endothelial cells expressing the chemokine CXCL12, but whether a separate niche instructs multipotent progenitor (MPP) differentiation remains unclear. We show that MPPs resided in HSC niches, where they encountered lineage-instructive differentiation signals. Conditional deletion of the chemokine receptor CXCR4 in MPPs reduced differentiation into common lymphoid progenitors (CLPs), which decreased lymphopoiesis...
December 20, 2016: Immunity
https://www.readbyqxmd.com/read/27846608/the-dna-sensing-aim2-inflammasome-controls-radiation-induced-cell-death-and-tissue-injury
#19
Bo Hu, Chengcheng Jin, Hua-Bing Li, Jiyu Tong, Xinshou Ouyang, Naniye Malli Cetinbas, Shu Zhu, Till Strowig, Fred C Lam, Chen Zhao, Jorge Henao-Mejia, Omer Yilmaz, Katherine A Fitzgerald, Stephanie C Eisenbarth, Eran Elinav, Richard A Flavell
Acute exposure to ionizing radiation induces massive cell death and severe damage to tissues containing actively proliferating cells, including bone marrow and the gastrointestinal tract. However, the cellular and molecular mechanisms underlying this pathology remain controversial. Here, we show that mice deficient in the double-stranded DNA sensor AIM2 are protected from both subtotal body irradiation-induced gastrointestinal syndrome and total body irradiation-induced hematopoietic failure. AIM2 mediates the caspase-1-dependent death of intestinal epithelial cells and bone marrow cells in response to double-strand DNA breaks caused by ionizing radiation and chemotherapeutic agents...
November 11, 2016: Science
https://www.readbyqxmd.com/read/27846573/a-pathogenic-role-for-t-cell-derived-il-22bp-in-inflammatory-bowel-disease
#20
Penelope Pelczar, Mario Witkowski, Laura Garcia Perez, Jan Kempski, Anna G Hammel, Leonie Brockmann, Dörte Kleinschmidt, Sandra Wende, Cathleen Haueis, Tanja Bedke, Marco Witkowski, Susanne Krasemann, Stefan Steurer, Carmen J Booth, Philipp Busch, Alexandra König, Ursula Rauch, Daniel Benten, Jakob R Izbicki, Thomas Rösch, Ansgar W Lohse, Till Strowig, Nicola Gagliani, Richard A Flavell, Samuel Huber
Intestinal inflammation can impair mucosal healing, thereby establishing a vicious cycle leading to chronic inflammatory bowel disease (IBD). However, the signaling networks driving chronic inflammation remain unclear. Here we report that CD4(+) T cells isolated from patients with IBD produce high levels of interleukin-22 binding protein (IL-22BP), the endogenous inhibitor of the tissue-protective cytokine IL-22. Using mouse models, we demonstrate that IBD development requires T cell-derived IL-22BP. Lastly, intestinal CD4(+) T cells isolated from IBD patients responsive to treatment with antibodies against tumor necrosis factor-α (anti-TNF-α), the most effective known IBD therapy, exhibited reduced amounts of IL-22BP expression but still expressed IL-22...
October 21, 2016: Science
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