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intestinal homeostasis

Yafei Duan, Yun Wang, Qingsong Liu, Dalin Xiong, Jiasong Zhang
Harmful effects of water pollutants are myriad. Sulfide from water bodies affects the aquatic animals. Intestine barrier function serves as the front-line of animals defense. Our previous study confirmed the toxic effect of sulfide on intestine immune response of Litopenaeus vannamei, but the underlying mechanisms remained elusive. Therefore, in this study, we investigated the transcriptomic and microbiota responses of the L. vannamei intestine subjected to acute sulfide exposure. Sulfide decreased bacterial richness and altered the intestine microbiota composition...
February 14, 2019: Fish & Shellfish Immunology
Imke Atreya, Markus Kindermann, Stefan Wirtz
Colorectal cancer (CRC) is a highly prominent cause of cancer-related deaths worldwide. Although the functions of immune cells in the colorectal tumor microenvironment are complex and heterogeneous, dysregulated changes in the composition and activation state of immune cells are believed to represent key events supporting the establishment of pro- or anti-tumorigenic immune states. Recently, innate lymphoid cells (ILCs) emerged as central innate immune mediators during both gastrointestinal homeostasis and inflammatory pathologies...
February 14, 2019: Seminars in Immunology
Hyoung-Soo Cho, Andrea Reboldi, Jason A Hall, Leslie J Berg
Innate lymphoid cells (ILC) are lymphocytes that lack an antigen-specific receptor and are preferentially localized in non-lymphoid tissues, such as mucosal barriers. In these locations ILC respond to tissue perturbations by producing factors that promote tissue repair and improve barrier integrity. We show that mice lacking the Tec kinase ITK have impaired intestinal tissue integrity, and a reduced ability to restore homeostasis after tissue damage. This defect is associated with a substantial loss of Type 2 ILC (ILC2) in the intestinal lamina propria...
February 15, 2019: Nature Communications
Lorenz Mittermeier, Lusine Demirkhanyan, Benjamin Stadlbauer, Andreas Breit, Camilla Recordati, Anne Hilgendorff, Masayuki Matsushita, Attila Braun, David G Simmons, Eleonora Zakharian, Thomas Gudermann, Vladimir Chubanov
Zn2+ , Mg2+ , and Ca2+ are essential minerals required for a plethora of metabolic processes and signaling pathways. Different categories of cation-selective channels and transporters are therefore required to tightly control the cellular levels of individual metals in a cell-specific manner. However, the mechanisms responsible for the organismal balance of these essential minerals are poorly understood. Herein, we identify a central and indispensable role of the channel-kinase TRPM7 for organismal mineral homeostasis...
February 15, 2019: Proceedings of the National Academy of Sciences of the United States of America
Yanan S Zhang, Dazhuan E Xin, Zhizhang Wang, Xinyang Song, Yanyun Sun, Quanli C Zou, Jichen Yue, Chenxi Zhang, Junxun M Zhang, Zhi Liu, Xiaoren Zhang, Ting C Zhao, Bing Su, Y Eugene Chin
T helper 17 (Th17)-cell differentiation triggered by interleukin-6 (IL-6) via STAT3 activation promotes inflammation in inflammatory bowel disease (IBD) patients. However, leukemia inhibitory factor (LIF), an IL-6 family cytokine, restricts inflammation by blocking Th17-cell differentiation via an unknown mechanism. Here, we report that microbiota dysregulation promotes LIF secretion by intestinal epithelial cells (IECs) in a mouse colitis model. LIF greatly activates STAT4 phosphorylation on multiple SPXX elements within the C-terminal transcription regulation domain...
February 15, 2019: EMBO Journal
Bijun Wen, Amel Taibi, Christopher R Villa, Shin-Hann Lee, Sofia Sagaidak, Elena M Comelli
In vitro and in vivo studies suggest that selected Bifidobacterium bifidum strains sustain intestinal homeostasis. This study aimed to examine whether the administration of B. bifidum MIMBb75 (BB75) attenuates Citrobacter rodentium infection, a murine model for enteric infection and inflammatory bowel disease in humans. C57Bl6/J mice were randomized to receive BB75 daily starting before or after C. rodentium infection. BB75 load and infection kinetics were monitored. On day 10 post-infection (p.i.), histological parameters of the large intestine were assessed...
February 14, 2019: Microorganisms
Federica Laudisi, Davide Di Fusco, Vincenzo Dinallo, Carmine Stolfi, Antonio Di Grazia, Irene Marafini, Alfredo Colantoni, Angela Ortenzi, Claudia Alteri, Francesca Guerrieri, Maria Mavilio, Francesca Ceccherini-Silberstein, Massimo Federici, Thomas Thornton MacDonald, Ivan Monteleone, Giovanni Monteleone
BACKGROUND & AIMS: Food additives, such as emulsifiers, stabilizers, or bulking agents, are present in the Western diet and their consumption is increasing. However, little is known about their potential effects on intestinal homeostasis. In this study we examined the effect of some of these food additives on gut inflammation. METHODS: Mice were given drinking water containing maltodextrin (MDX), propylene glycol, or animal gelatin, and then challenged with dextran sulfate sodium or indomethacin...
September 11, 2018: Cellular and Molecular Gastroenterology and Hepatology
Sabah Haq, Jensine Grondin, Suhrid Banskota, Waliul I Khan
The intestinal mucosa is a site of multiple stressors and forms the barrier between the internal and external environment. In the intestine, a complex interplay between the microbiota, epithelial barrier and the local immune system maintains homeostasis and promotes a healthy gut. One of the major cellular catabolic processes that regulate this homeostasis is autophagy. Autophagy is required to maintain anti-microbial defense, epithelial barrier integrity and mucosal immune response. Dysregulation of the autophagy process causes disruption of several aspects of the intestinal epithelium and the immune system that can lead to an inappropriate immune response and subsequent inflammation...
February 14, 2019: Journal of Biomedical Science
Lianne de Haan, Sarah J van der Lely, Anne-Loes K Warps, Quincy Hofsink, Pim B Olthof, Mark J de Keijzer, Daniël A Lionarons, Lionel Mendes-Dias, Bote G Bruinsma, Korkut Uygun, Hartmut Jaeschke, Geoffrey C Farrell, Narci Teoh, Rowan F van Golen, Tiangang Li, Michal Heger
Background: Liver regeneration following partial hepatectomy (PHx) is a complicated process involving multiple organs and several types of signaling networks. The bile acid-activated metabolic pathways occupy an auxiliary yet important chapter in the entire biochemical story. PHx is characterized by rapid but transient bile acid overload in the liver, which constitutes the first wave of proliferative signaling in the remnant hepatocytes. Bile acids trigger hepatocyte proliferation through activation of several nuclear receptors...
May 28, 2018: Journal of Clinical and Translational Research
Tian Deng, Caixia Suo, Jiali Chang, Rui Yang, Jingyu Li, Ting Cai, Ju Qiu
OX40L is one of the co-stimulatory molecules that can be expressed by splenic lymphoid tissue inducer (Lti) cells, a subset of group 3 innate lymphoid cells (ILC3s). OX40L expression in subsets of intestinal ILC3s and the molecular regulation of OX40L expression in ILC3s are unknown. Here, we showed intestinal ILC3s marked as an OX40Lhigh population among all the intestinal leukocytes and were the dominant source of OX40L in Rag1-/- mice. All ILC3 subsets expressed OX40L, and NCR- ILC3s were the most abundant source of OX40L...
February 13, 2019: Cellular & Molecular Immunology
Michael Platten, Ellen A A Nollen, Ute F Röhrig, Francesca Fallarino, Christiane A Opitz
L-Tryptophan (Trp) metabolism through the kynurenine pathway (KP) is involved in the regulation of immunity, neuronal function and intestinal homeostasis. Imbalances in Trp metabolism in disorders ranging from cancer to neurodegenerative disease have stimulated interest in therapeutically targeting the KP, particularly the main rate-limiting enzymes indoleamine-2,3-dioxygenase 1 (IDO1), IDO2 and tryptophan-2,3-dioxygenase (TDO) as well as kynurenine monooxygenase (KMO). However, although small-molecule IDO1 inhibitors showed promise in early-stage cancer immunotherapy clinical trials, a phase III trial was negative...
February 13, 2019: Nature Reviews. Drug Discovery
David M Gay, Rachel A Ridgway, Miryam Müeller, Michael C Hodder, Ann Hedley, William Clark, Joshua D Leach, Rene Jackstadt, Colin Nixon, David J Huels, Andrew D Campbell, Thomas G Bird, Owen J Sansom
Different thresholds of Wnt signalling are thought to drive stem cell maintenance, regeneration, differentiation and cancer. However, the principle that oncogenic Wnt signalling could be specifically targeted remains controversial. Here we examine the requirement of BCL9/9l, constituents of the Wnt-enhanceosome, for intestinal transformation following loss of the tumour suppressor APC. Although required for Lgr5+ intestinal stem cells and regeneration, Bcl9/9l deletion has no impact upon normal intestinal homeostasis...
February 13, 2019: Nature Communications
Ting Guo, Zi Nan, Chen Miao, Xiaoye Jin, Weiwei Yang, Zehua Wang, Yinqi Tu, Hongcun Bao, Jialan Lyu, Huimei Zheng, Qiannan Deng, Pengfei Guo, Yongmei Xi, Xiaohang Yang, Wanzhong Ge
Atg101 is an autophagy-related gene identified in worms, flies, mice, and mammals and encodes a protein that functions in autophagosome formation by associating with the ULK1-Atg13-Fip200 complex. In the last few years, the critical role of Atg101 in autophagy has been well established through biochemical studies and the determination of its protein structure. However, Atg101's physiological role both during development and in adulthood remains less understood. Here, we describe the generation and characterization of an Atg101 loss-of-function mutant in Drosophila and report on the roles of Atg101 in maintaining tissue homeostasis in both adult brains and midguts...
February 13, 2019: Journal of Biological Chemistry
Peter Allan Dobranowski, Chris Tang, Jean Philippe Sauvé, Susan Christine Menzies, Laura May Sly
Inflammatory bowel disease, encompassing both ulcerative colitis and Crohn's disease, is characterized by chronic, relapsing-remitting gastrointestinal inflammation of unknown etiology. SHIP deficient mice develop fully penetrant, spontaneous ileitis at 6 weeks of age, and thus offer a tractable model of Crohn's disease-like inflammation. Since disruptions to the microbiome are implicated in the pathogenesis of Crohn's disease, we conducted a 16S rRNA gene survey of the ileum, cecum, colon, and stool contents of SHIP+/+ and SHIP-/- mice...
February 13, 2019: Gut Microbes
T M Zaved Waise, Mozhgan Rasti, Frank A Duca, Song-Yang Zhang, Paige V Bauer, Christopher J Rhodes, Tony K T Lam
Glucose homeostasis is partly controlled by the energy sensor mechanistic target of rapamycin (mTOR) in the muscle and liver. However, whether mTOR in the small intestine affects glucose homeostasis in vivo remains unknown. Here, we first report that delivery of rapamycin or an adenovirus encoding the dominant negative acting mTOR-mutated protein into the upper small intestine is sufficient to inhibit small intestinal mTOR signaling and lower glucose production in rodents with high fat diet-induced insulin resistance...
February 12, 2019: Nature Communications
Hisako Kayama, Haruka Tani, Shoko Kitada, Anunya Opasawatchai, Ryu Okumura, Daisuke Motooka, Shota Nakamura, Kiyoshi Takeda
Inappropriate activation of the interleukin (IL)-23 signaling pathway causes chronic inflammation through the induction of immunopathological Th17 cells in several tissues including the intestine, whereas adequate Th17 responses are essential for host defense against harmful organisms. In the intestinal lamina propria, IL-23 is primarily produced by innate myeloid cells including dendritic cells (DCs) and macrophages (Ms). However, the molecular mechanisms underlying the regulation of IL-23 production by these cells remains poorly understood...
February 12, 2019: International Immunology
P Moulin, V Rong, A Ribeiro E Silva, V G Pederick, E Camiade, L Mereghetti, C A McDevitt, A Hiron
Streptococcus agalactiae is part of the human intestinal and uro-genital microbiota, but also a leading cause of septicemia and meningitis in neonates. Its ability to cause disease depends upon the acquisition of nutrients from its environment, including the transition metal ion zinc. The primary zinc acquisition system of the pathogen is the Adc/Lmb ABC permease, which is essential for viability in zinc-restricted environments. Here, we show that in addition to the AdcCB transporter, and the three zinc-binding proteins, Lmb, AdcA and AdcAII, S...
February 11, 2019: Journal of Bacteriology
Mercé Albert-Bayo, Irene Paracuellos, Ana M González-Castro, Amanda Rodríguez-Urrutia, María J Rodríguez-Lagunas, Carmen Alonso-Cotoner, Javier Santos, María Vicario
The gastrointestinal tract harbours the largest population of mast cells in the body; this highly specialised leukocyte cell type is able to adapt its phenotype and function to the microenvironment in which it resides. Mast cells react to external and internal stimuli thanks to the variety of receptors they express, and carry out effector and regulatory tasks by means of the mediators of different natures they produce. Mast cells are fundamental elements of the intestinal barrier as they regulate epithelial function and integrity, modulate both innate and adaptive mucosal immunity, and maintain neuro-immune interactions, which are key to functioning of the gut...
February 8, 2019: Cells
Annika Wyss, Tina Raselli, Nathan Perkins, Florian Ruiz, Gérard Schmelczer, Glynis Klinke, Anja Moncsek, René Roth, Marianne R Spalinger, Larissa Hering, Kirstin Atrott, Silvia Lang, Isabelle Frey-Wagner, Joachim C Mertens, Michael Scharl, Andreas W Sailer, Oliver Pabst, Martin Hersberger, Caroline Pot, Gerhard Rogler, Benjamin Misselwitz
The gene encoding for Epstein-Barr virus-induced G-protein-coupled receptor 2 (EBI2) is a risk gene for inflammatory bowel disease (IBD). Together with its oxysterol ligand 7α,25-dihydroxycholesterol, EBI2 mediates migration and differentiation of immune cells. However, the role of EBI2 in the colonic immune system remains insufficiently studied. We found increased mRNA expression of EBI2 and oxysterol-synthesizing enzymes (CH25H, CYP7B1) in the inflamed colon of patients with ulcerative colitis and mice with acute or chronic dextran sulfate sodium (DSS) colitis...
February 11, 2019: Mucosal Immunology
Koichi Kurata, Hideaki Kawahara, Kohji Nishimura, Mitsuo Jisaka, Kazushige Yokota, Hidehisa Shimizu
Intestinal bacteria produce skatole (3-methylindole) from tryptophan in dietary proteins and ingesting large quantities of animal protein is associated with increased fecal skatole concentrations. Although possibly associated with disrupted intestinal homeostasis, the influence of skatole on intestinal epithelial cellular function has not been characterized in detail. The present study aimed to determine whether skatole induces intestinal epithelial cell (IEC) dysfunction. We found that skatole dose-dependently caused IEC death and time-dependently induced IEC apoptosis...
February 7, 2019: Biochemical and Biophysical Research Communications
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