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regulatory macrophage

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https://www.readbyqxmd.com/read/28738016/eomesodermin-promotes-the-development-of-type-1-regulatory-t-tr1-cells
#1
Ping Zhang, Jason S Lee, Kate H Gartlan, Iona S Schuster, Iain Comerford, Antiopi Varelias, Md Ashik Ullah, Slavica Vuckovic, Motoko Koyama, Rachel D Kuns, Kelly R Locke, Kirrilee J Beckett, Stuart D Olver, Luke D Samson, Marcela Montes de Oca, Fabian de Labastida Rivera, Andrew D Clouston, Gabrielle T Belz, Bruce R Blazar, Kelli P MacDonald, Shaun R McColl, Ranjeny Thomas, Christian R Engwerda, Mariapia A Degli-Esposti, Axel Kallies, Siok-Keen Tey, Geoffrey R Hill
Type 1 regulatory T (TR1) cells are Foxp3(-) interleukin-10 (IL-10)-producing CD4(+) T cells with potent immunosuppressive properties, but their requirements for lineage development have remained elusive. We show that TR1 cells constitute the most abundant regulatory population after allogeneic bone marrow transplantation (BMT), express the transcription factor Eomesodermin (Eomes), and are critical for the prevention of graft-versus-host disease. We demonstrate that Eomes is required for TR1 cell differentiation, during which it acts in concert with the transcription factor B lymphocyte-induced maturation protein-1 (Blimp-1) by transcriptionally activating IL-10 expression and repressing differentiation into other T helper cell lineages...
April 7, 2017: Science Immunology
https://www.readbyqxmd.com/read/28736205/developmental-and-extrahepatic-physiological-functions-of-srebp-pathway-genes-in-mice
#2
REVIEW
Luke J Engelking, Mary Jo Cantoria, Yanchao Xu, Guosheng Liang
Sterol regulatory element-binding proteins (SREBPs), master transcriptional regulators of cholesterol and fatty acid synthesis, have been found to contribute to a diverse array of cellular processes. In this review, we focus on genetically engineered mice in which the activities of six components of the SREBP gene pathway, namely SREBP-1, SREBP-2, Scap, Insig-1, Insig-2, or Site-1 protease have been altered through gene knockout or transgenic approaches. In addition to the expected impacts on lipid metabolism, manipulation of these genes in mice is found to affect a wide array of developmental and physiologic processes ranging from interferon signaling in macrophages to synaptic transmission in the brain...
July 20, 2017: Seminars in Cell & Developmental Biology
https://www.readbyqxmd.com/read/28736203/oral-administration-of-visceral-adipose-tissue-antigens-ameliorates-metabolic-disorders-in-mice-and-elevates-visceral-adipose-tissue-resident-cd4-cd25-foxp3-regulatory-t-cells
#3
Xiangyu Chen, Dali Zhang, Xiaoling Chen, Gang Meng, Qian Zheng, Wenli Mai, Yuzhang Wu, Lilin Ye, Li Wang
Obesity and type 2 diabetes are linked with chronic, low-grade inflammation in visceral adipose tissue (VAT). A unique population of VAT-resident CD4(+)Foxp3(+) Tregs plays a crucial role in regulating VAT inflammation and metabolic homeostasis. VAT-resident Tregs display a highly restricted TCR repertoire, suggesting they recognize certain autoantigen(s) in VAT. A dramatic reduction of VAT-resident Tregs has been shown to closely correlate with obesity-related VAT chronic inflammation and metabolic disorders...
July 20, 2017: Vaccine
https://www.readbyqxmd.com/read/28735095/regulation-of-lipid-droplet-associated-proteins-by-peroxisome-proliferator-activated-receptors
#4
REVIEW
Montserrat A de la Rosa Rodriguez, Sander Kersten
Excess fatty acids are stored in cells as triglycerides in specialized organelles called lipid droplets (LD). LD can be found in nearly all cell types and may expand during certain (patho)physiological conditions. The synthesis and breakdown of triglycerides and their deposition in LD is governed by a diverse set of enzymes and LD-associated proteins. These proteins serve structural roles in and around LD and regulate the activity of key lipogenic and lipolytic enzymes. The LD-associated proteins are subject to multiple regulatory mechanisms at the protein and gene expression level...
July 19, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28733560/mir-122-socs1-jak2-axis-regulates-allergic-inflammation-and-allergic-inflammation-promoted-cellular-interactions
#5
Kyeonga Noh, Misun Kim, Youngmi Kim, Hanearl Kim, Hyuna Kim, Jaehwan Byun, Yeongseo Park, Hansoo Lee, Yun Sil Lee, Jongseon Choe, Young Myeong Kim, Dooil Jeoung
The regulatory role of suppressor of cytokine signaling 1 (SOCS1) in inflammation has been reported. However, its role in allergic inflammation has not been previously reported. SOCS1 mediated in vitro and in vivo allergic inflammation. Histone deacetylase-3 (HDAC3), a mediator of allergic inflammation, interacted with SOCS1, and miR-384 inhibitor, a positive regulator of HDAC3, induced features of allergic inflammation in an SOCS1-dependent manner. miRNA array analysis showed that the expression of miR-122 was decreased by antigen-stimulation...
July 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/28728794/myeloid-suppressor-cells-in-cancer-and-autoimmunity
#6
REVIEW
Antonio Sica, Marco Massarotti
A bottleneck for immunotherapy of cancer is the immunosuppressive microenvironment in which the tumor cells proliferate. Cancers harness the immune regulatory mechanism that prevents autoimmunity from evading immunosurveillance and promoting immune destruction. Regulatory T cells, myeloid suppressor cells, inhibitory cytokines and immune checkpoint receptors are the major components of the immune system acting in concert with cancer cells and causing the subversion of anti-tumor immunity. This redundant immunosuppressive network poses an impediment to efficacious immunotherapy by facilitating tumor progression...
July 17, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28723546/local-modulation-of-antigen-presenting-cell-development-after-resolution-of-pneumonia-induces-long-term-susceptibility-to-secondary-infections
#7
Antoine Roquilly, Hamish E G McWilliam, Cedric Jacqueline, Zehua Tian, Raphael Cinotti, Marie Rimbert, Linda Wakim, Irina Caminschi, Mireille H Lahoud, Gabrielle T Belz, Axel Kallies, Justine D Mintern, Karim Asehnoune, Jose A Villadangos
Lung infections cause prolonged immune alterations and elevated susceptibility to secondary pneumonia. We found that, after resolution of primary viral or bacterial pneumonia, dendritic cells (DC), and macrophages exhibited poor antigen-presentation capacity and secretion of immunogenic cytokines. Development of these "paralyzed" DCs and macrophages depended on the immunosuppressive microenvironment established upon resolution of primary infection, which involved regulatory T (Treg) cells and the cytokine TGF-β...
July 18, 2017: Immunity
https://www.readbyqxmd.com/read/28720729/inhibition-of-inflammasome-dependent-interleukin-1%C3%AE-production-by-streptococcal-nad-glycohydrolase-evidence-for-extracellular-activity
#8
Dóra Hancz, Elsa Westerlund, Benedicte Bastiat-Sempe, Onkar Sharma, Christine Valfridsson, Lena Meyer, John F Love, Maghnus O'Seaghdha, Michael R Wessels, Jenny J Persson
Group A Streptococcus (GAS) is a common human pathogen and the etiologic agent of a large number of diseases ranging from mild, self-limiting infections to invasive life-threatening conditions. Two prominent virulence factors of this bacterium are the genetically and functionally linked pore-forming toxin streptolysin O (SLO) and its cotoxin NAD(+)-glycohydrolase (NADase). Overexpression of these toxins has been linked to increased bacterial virulence and is correlated with invasive GAS disease. NADase can be translocated into host cells by a SLO-dependent mechanism, and cytosolic NADase has been assigned multiple properties such as protection of intracellularly located GAS bacteria and induction of host cell death through energy depletion...
July 18, 2017: MBio
https://www.readbyqxmd.com/read/28720426/langerhans-cells-the-macrophage-in-dendritic-cell-clothing
#9
REVIEW
Thomas Doebel, Benjamin Voisin, Keisuke Nagao
Our assumptions on the identity and functions of Langerhans cells (LCs) of the epidermis have undergone considerable changes. Once thought to be prototypic representatives of the dendritic cell (DC) lineage, they are now considered to be a specialized subset of tissue-resident macrophages. Despite this, LCs display a remarkable mixture of properties. Like many tissue macrophages, they self-maintain locally. However, unlike tissue macrophages and similar to DCs, they homeostatically migrate to lymph nodes and present antigen to antigen-specific T cells...
July 15, 2017: Trends in Immunology
https://www.readbyqxmd.com/read/28716985/two-microrna-signatures-for-malignancy-and-immune-infiltration-predict-overall-survival-in-advanced-epithelial-ovarian-cancer
#10
Ilya Korsunsky, Janaki Parameswaran, Iuliana Shapira, John Lovecchio, Andrew Menzin, Jill Whyte, Lisa Dos Santos, Sharon Liang, Tawfiqul Bhuiya, Mary Keogh, Houman Khalili, Cassandra Pond, Anthony Liew, Andrew Shih, Peter K Gregersen, Annette T Lee
MicroRNAs have been established as key regulators of tumor gene expression and as prime biomarker candidates for clinical phenotypes in epithelial ovarian cancer (EOC). We analyzed the coexpression and regulatory structure of microRNAs and their co-localized gene targets in primary tumor tissue of 20 patients with advanced EOC in order to construct a regulatory signature for clinical prognosis. We performed an integrative analysis to identify two prognostic microRNA/mRNA coexpression modules, each enriched for consistent biological functions...
July 17, 2017: Journal of Investigative Medicine: the Official Publication of the American Federation for Clinical Research
https://www.readbyqxmd.com/read/28716827/galectin-1-driven-tolerogenic-programs-aggravate-yersinia-enterocolitica-infection-by-repressing-antibacterial-immunity
#11
Roberto C Davicino, Santiago P Méndez-Huergo, Ricardo J Eliçabe, Juan C Stupirski, Ingo Autenrieth, María S Di Genaro, Gabriel A Rabinovich
Yersinia enterocolitica is an enteropathogenic bacterium that causes gastrointestinal disorders, as well as extraintestinal manifestations. To subvert the host's immune response, Y. enterocolitica uses a type III secretion system consisting of an injectisome and effector proteins, called Yersinia outer proteins (Yops), that modulate activation, signaling, and survival of immune cells. In this article, we show that galectin-1 (Gal-1), an immunoregulatory lectin widely expressed in mucosal tissues, contributes to Y...
July 17, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28716484/the-anti-tumor-activity-of-the-stat3-inhibitor-stx-0119-occurs-via-promotion-of-tumor-infiltrating-lymphocyte-accumulation-in-temozolomide-resistant-glioblastoma-cell-line
#12
Yasuto Akiyama, Chizu Nonomura, Tadashi Ashizawa, Akira Iizuka, Ryota Kondou, Haruo Miyata, Takashi Sugino, Koichi Mitsuya, Nakamasa Hayashi, Yoko Nakasu, Akira Asai, Mamoru Ito, Yoshio Kiyohara, Ken Yamaguchi
STAT3 is considered to be a key molecule to mediating tumor-induced immunosuppression in various manners at tumor sites, by acting through immune-regulatory cytokines derived from the tumor cells. Specific anti-STAT3 inhibitors have been developed using nude mouse models transplanted with human tumor cells. However, mouse systems cannot accurately represent the human immune response induced by STAT3 inhibitors, and more humanized therapeutic model based on human immune cells and tumors are needed. In the present study, an immune-deficient NOG mouse with the deletion of both MHC-class I and class II genes, an MHC-double knockout mouse (dKO-NOG), was developed and used to establish humanized immunotherapeutic model...
July 15, 2017: Immunology Letters
https://www.readbyqxmd.com/read/28716104/evaluating-the-potential-of-gold-silver-and-silica-nanoparticles-to-saturate-mononuclear-phagocytic-system-tissues-under-repeat-dosing-conditions
#13
James L Weaver, Grainne A Tobin, Taylor Ingle, Simona Bancos, David Stevens, Rodney Rouse, Kristina E Howard, David Goodwin, Alan Knapton, Xiaohong Li, Katherine Shea, Sharron Stewart, Lin Xu, Peter L Goering, Qin Zhang, Paul C Howard, Jessie Collins, Saeed Khan, Kidon Sung, Katherine M Tyner
BACKGROUND: As nanoparticles (NPs) become more prevalent in the pharmaceutical industry, questions have arisen from both industry and regulatory stakeholders about the long term effects of these materials. This study was designed to evaluate whether gold (10 nm), silver (50 nm), or silica (10 nm) nanoparticles administered intravenously to mice for up to 8 weeks at doses known to be sub-toxic (non-toxic at single acute or repeat dosing levels) and clinically relevant could produce significant bioaccumulation in liver and spleen macrophages...
July 17, 2017: Particle and Fibre Toxicology
https://www.readbyqxmd.com/read/28713774/epic-immune-battles-of-history-neutrophils-vs-staphylococcus-aureus
#14
REVIEW
Fermin E Guerra, Timothy R Borgogna, Delisha M Patel, Eli W Sward, Jovanka M Voyich
Neutrophils are the most abundant leukocytes in human blood and the first line of defense after bacteria have breached the epithelial barriers. After migration to a site of infection, neutrophils engage and expose invading microorganisms to antimicrobial peptides and proteins, as well as reactive oxygen species, as part of their bactericidal arsenal. Ideally, neutrophils ingest bacteria to prevent damage to surrounding cells and tissues, kill invading microorganisms with antimicrobial mechanisms, undergo programmed cell death to minimize inflammation, and are cleared away by macrophages...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/28710436/epithelial-derived-il-33-promotes-intestinal-tumorigenesis-in-apc-min-mice
#15
Zhengxiang He, Lili Chen, Fabricio O Souto, Claudia Canasto-Chibuque, Gerold Bongers, Madhura Deshpande, Noam Harpaz, Huaibin M Ko, Kevin Kelley, Glaucia C Furtado, Sergio A Lira
Increased expression of Interleukin (IL)-33 has been detected in intestinal samples of patients with ulcerative colitis, a condition associated with increased risk for colon cancer, but its role in the development of colorectal cancer has yet to be fully examined. Here, we investigated the role of epithelial expressed IL-33 during development of intestinal tumors. IL-33 expression was detected in epithelial cells in colorectal cancer specimens and in the Apc (Min/+) mice. To better understand the role of epithelial-derived IL-33 in the intestinal tumorigenesis, we generated transgenic mice expressing IL-33 in intestinal epithelial cells (V33 mice)...
July 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28708287/regulation-of-rankl-induced-osteoclastogenesis-by-ring-finger-protein-rnf114
#16
Boren Lin, Qi Ke, Douglas W Leaman, Vijay Goel, Anand Agarwal
Normal bone remodeling is a continuous process orchestrated by bone-resorbing osteoclasts and bone-forming osteoblasts, which an imbalance in bone remodeling results in metabolic bone diseases. RANKL, a member of the TNF cytokine family, functions as a key stimulator for osteoclast differentiation and maturation. Here, we report that RNF114, previously identified as a psoriasis susceptibility gene, plays a regulatory role in the RANKL/RANK/TRAF6 signaling pathway that mediates osteoclastogenesis. Our results demonstrated that RNF114 expression was significantly down-regulated in mouse osteoclast precursor cells undergoing RANKL-induced osteoclast differentiation...
July 14, 2017: Journal of Orthopaedic Research: Official Publication of the Orthopaedic Research Society
https://www.readbyqxmd.com/read/28701870/nuclear-factor-kappa-b-and-activator-protein-1-mediated-immunostimulatory-activity-of-compound-k-in-monocytes-and-macrophages
#17
Woo Seok Yang, Young-Su Yi, Donghyun Kim, Min Ho Kim, Jae Gwang Park, Eunji Kim, Sang Yeol Lee, Keejung Yoon, Jong-Hoon Kim, Junseong Park, Jae Youl Cho
BACKGROUND: Compound K (CK) is a bioactive derivative of ginsenoside Rb1 in Panax ginseng (Korean ginseng). Its biological and pharmacological activities have been studied in various disease conditions, although its immunomodulatory role in innate immunity mediated by monocytes/macrophages has been poorly understood. In this study, we aimed to elucidate the regulatory role of CK on cellular events mediated by monocytes and macrophages in innate immune responses. METHODS: The immunomodulatory role of CK was explored by various immunoassays including cell-cell adhesion, fibronectin adhesion, cell migration, phagocytic uptake, costimulatory molecules, reactive oxygen species production, luciferase activity, and by the measurement of mRNA levels of proinflammatory genes...
July 2017: Journal of Ginseng Research
https://www.readbyqxmd.com/read/28699638/bcat1-controls-metabolic-reprogramming-in-activated-human-macrophages-and-is-associated-with-inflammatory-diseases
#18
Adonia E Papathanassiu, Jeong-Hun Ko, Martha Imprialou, Marta Bagnati, Prashant K Srivastava, Hong A Vu, Danilo Cucchi, Stephen P McAdoo, Elitsa A Ananieva, Claudio Mauro, Jacques Behmoaras
Branched-chain aminotransferases (BCAT) are enzymes that initiate the catabolism of branched-chain amino acids (BCAA), such as leucine, thereby providing macromolecule precursors; however, the function of BCATs in macrophages is unknown. Here we show that BCAT1 is the predominant BCAT isoform in human primary macrophages. We identify ERG240 as a leucine analogue that blocks BCAT1 activity. Selective inhibition of BCAT1 activity results in decreased oxygen consumption and glycolysis. This decrease is associated with reduced IRG1 levels and itaconate synthesis, suggesting involvement of BCAA catabolism through the IRG1/itaconate axis within the tricarboxylic acid cycle in activated macrophages...
July 12, 2017: Nature Communications
https://www.readbyqxmd.com/read/28698597/selenoprotein-msrb1-promotes-anti-inflammatory-cytokine-gene-expression-in-macrophages-and-controls-immune-response-in-vivo
#19
Byung Cheon Lee, Sang-Goo Lee, Min-Kyung Choo, Ji Hyung Kim, Hae Min Lee, Sorah Kim, Dmitri E Fomenko, Hwa-Young Kim, Jin Mo Park, Vadim N Gladyshev
Post-translational redox modification of methionine residues often triggers a change in protein function. Emerging evidence points to this reversible protein modification being an important regulatory mechanism under various physiological conditions. Reduction of oxidized methionine residues is catalyzed by methionine sulfoxide reductases (Msrs). Here, we show that one of these enzymes, a selenium-containing MsrB1, is highly expressed in immune-activated macrophages and contributes to shaping cellular and organismal immune responses...
July 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28698173/interferon-regulatory-factor-5-controls-necrotic-core-formation-in-atherosclerotic-lesions-by-impairing-efferocytosis
#20
Anusha N Seneviratne, Andreas O Edsfeldt, Jennifer E Cole, Christina Kassiteridi, Maarten Swart, Inhye Park, Patricia Green, Tariq E Khoyratty, David G Saliba, Michael E Goddard, Stephen N Sansom, Isabel Goncalves, Rob Krams, Irina A Udalova, Claudia Monaco
Background -Myeloid cells are central to atherosclerotic lesion development and vulnerable plaque formation. Impaired ability of arterial phagocytes to uptake apoptotic cells (efferocytosis), promotes lesion growth and establishment of a necrotic core. The transcription factor Interferon Regulatory Factor (IRF)-5 is an important modulator of myeloid function and programming. We sought to investigate whether IRF5 affects the formation and phenotype of atherosclerotic lesions. Methods -We investigated the role of IRF5 in atherosclerosis in two complementary models...
July 11, 2017: Circulation
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