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https://www.readbyqxmd.com/read/29434592/signaling-lymphocyte-activation-molecule-family-5-enhances-autophagy-and-fine-tunes-cytokine-response-in-monocyte-derived-dendritic-cells-via-stabilization-of-interferon-regulatory-factor-8
#1
Zsofia Agod, Kitti Pazmandi, Dora Bencze, Gyorgy Vereb, Tamas Biro, Attila Szabo, Eva Rajnavolgyi, Attila Bacsi, Pablo Engel, Arpad Lanyi
Signaling lymphocyte activation molecule family (SLAMF) receptors are essential regulators of innate and adaptive immune responses. The function of SLAMF5/CD84, a family member with almost ubiquitous expression within the hematopoietic lineage is poorly defined. In this article, we provide evidence that in human monocyte-derived dendritic cells (moDCs) SLAMF5 increases autophagy, a degradative pathway, which is highly active in dendritic cells (DCs) and plays a critical role in orchestration of the immune response...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29385873/dysfunction-of-trim21-in-interferon-signature-of-systemic-lupus-erythematosus
#2
Reikou Kamiyama, Ryusuke Yoshimi, Mitsuhiro Takeno, Yasuhiro Iribe, Toshinori Tsukahara, Daiga Kishimoto, Yosuke Kunishita, Yumiko Sugiyama, Naomi Tsuchida, Hiroto Nakano, Kaoru Minegishi, Maasa Tamura, Yukiko Asami, Yohei Kirino, Yoshiaki Ishigatsubo, Keiko Ozato, Hideaki Nakajima
OBJECTIVES: TRIM21 is an E3 ubiquitin ligase for interferon regulatory factors (IRFs) that are involved in innate and acquired immunity. Here we evaluated the role of TRIM21 in the interferon (IFN) signature of systemic lupus erythematosus (SLE). METHODS: Twenty SLE patients and 24 healthy controls were enrolled in this study. We analyzed mRNA expression of TRIM21, type I IFN, and IFN-inducible genes in peripheral blood mononuclear cell (PBMCs). The protein levels of IRFs were assessed by Western blotting in PBMCs cultured with or without MG-132...
February 1, 2018: Modern Rheumatology
https://www.readbyqxmd.com/read/29290826/a-cell-penetrating-whole-molecule-antibody-targeting-intracellular-hbx-suppresses-hepatitis-b-virus-via-trim21-dependent-pathway
#3
Jun-Fang Zhang, Hua-Long Xiong, Jia-Li Cao, Shao-Juan Wang, Xue-Ran Guo, Bi-Yun Lin, Ying Zhang, Jing-Hua Zhao, Ying-Bin Wang, Tian-Ying Zhang, Quan Yuan, Jun Zhang, Ning-Shao Xia
Rationale: Monoclonal antibodies (mAbs) mostly targeting extracellular or cell surface molecules have been widely used in the treatment of various diseases. However, mAbs cannot pass through the cell membrane as efficiently as small compounds, thus limiting their use against intracellular targets. Methods to shuttle antibodies into living cells may largely expand research and application in areas based on mAbs. Hepatitis B virus X protein (HBx) is an important intracellular multi-functional viral protein in the life cycle of hepatitis B virus (HBV)...
2018: Theranostics
https://www.readbyqxmd.com/read/29261807/characterization-of-host-proteins-interacting-with-the-lymphocytic-choriomeningitis-virus-l-protein
#4
Kseniya Khamina, Alexander Lercher, Michael Caldera, Christopher Schliehe, Bojan Vilagos, Mehmet Sahin, Lindsay Kosack, Anannya Bhattacharya, Peter Májek, Alexey Stukalov, Roberto Sacco, Leo C James, Daniel D Pinschewer, Keiryn L Bennett, Jörg Menche, Andreas Bergthaler
RNA-dependent RNA polymerases (RdRps) play a key role in the life cycle of RNA viruses and impact their immunobiology. The arenavirus lymphocytic choriomeningitis virus (LCMV) strain Clone 13 provides a benchmark model for studying chronic infection. A major genetic determinant for its ability to persist maps to a single amino acid exchange in the viral L protein, which exhibits RdRp activity, yet its functional consequences remain elusive. To unravel the L protein interactions with the host proteome, we engineered infectious L protein-tagged LCMV virions by reverse genetics...
December 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/29158558/protein-arginine-methyltransferase-5-has-prognostic-relevance-and-is-a-druggable-target-in-multiple-myeloma
#5
A Gullà, T Hideshima, G Bianchi, M Fulciniti, M Kemal Samur, J Qi, Y-T Tai, T Harada, E Morelli, N Amodio, R Carrasco, P Tagliaferri, N C Munshi, P Tassone, K C Anderson
Arginine methyltransferases critically regulate cellular homeostasis by modulating the functional outcome of their substrates. The protein arginine methyltransferase 5 (PRMT5) is an enzyme involved in growth and survival pathways promoting tumorigenesis. However, little is known about the biologic function of PRMT5 and its therapeutic potential in multiple myeloma (MM). In the present study, we identified and validated PRMT5 as a new therapeutic target in MM. PRMT5 is overexpressed in patient MM cells and associated with decreased progression-free survival and overall survival...
November 21, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/29113905/tripartite-motif-containing-trim-21-negatively-regulates-intestinal-mucosal-inflammation-through-inhibiting-th1-th17%C3%A2-cell-differentiation-in-patients-with-inflammatory-bowel-diseases
#6
Guangxi Zhou, Wei Wu, Lin Yu, Tianming Yu, Wenjing Yang, Ping Wang, Xiaoping Zhang, Yingzi Cong, Zhanju Liu
BACKGROUND: Tripartite motif-containing (TRIM) 21 has been implicated in the pathogenesis of several types of autoimmune diseases. OBJECTIVE: We sought to elucidate TRIM21 expression in patients with inflammatory bowel diseases (IBDs) and its role in regulating intestinal mucosal inflammation. METHODS: TRIM21 expression was analyzed in the inflamed mucosa of patients with IBDs by means of quantitative RT-PCR and immunohistochemistry. Peripheral blood CD4+ T cells were transfected with lentivirus-expressing TRIM21 (LV-TRIM21) or LV-sh-TRIM21, and cytokine expression was determined by using quantitative RT-PCR and ELISA...
November 4, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/29038421/stabilization-of-phosphofructokinase-1-platelet-isoform-by-akt-promotes-tumorigenesis
#7
Jong-Ho Lee, Rui Liu, Jing Li, Chuanbao Zhang, Yugang Wang, Qingsong Cai, Xu Qian, Yan Xia, Yanhua Zheng, Yuji Piao, Qianming Chen, John F de Groot, Tao Jiang, Zhimin Lu
Phosphofructokinase 1 (PFK1) plays a critical role in glycolysis; however, its role and regulation in tumorigenesis are not well understood. Here, we demonstrate that PFK1 platelet isoform (PFKP) is the predominant PFK1 isoform in human glioblastoma cells and its expression correlates with total PFK activity. We show that PFKP is overexpressed in human glioblastoma specimens due to an increased stability, which is induced by AKT activation resulting from phosphatase and tensin homologue (PTEN) loss and EGFR-dependent PI3K activation...
October 16, 2017: Nature Communications
https://www.readbyqxmd.com/read/29016728/augmented-th17-differentiation-in-trim21-deficiency-promotes-a-stable-phenotype-of-atherosclerotic-plaques-with-high-collagen-content
#8
Susanna Brauner, Xintong Jiang, Gudny Ella Thorlacius, Anna M Lundberg, Therese Östberg, Zhong-Qun Yan, Vijay K Kuchroo, Göran K Hansson, Marie Wahren-Herlenius
Aims: Patients with hyperlipidemia are at risk of atherosclerosis, but not all develop cardiovascular disease, highlighting the importance of other risk factors such as inflammation. Both the innate and adaptive arms of the immune system have been suggested in the initiation and propagation of plaque formation. Tri-partite motif (TRIM) 21 is a regulator of tissue inflammation and pro-inflammatory cytokine production, and has been implicated in chronic inflammatory disease. Here, we investigate a potential role for TRIM21 in coronary artery disease...
September 4, 2017: Cardiovascular Research
https://www.readbyqxmd.com/read/28968760/detection-of-host-response-to-viral-respiratory-infection-by-measurement-of-mrna-for-mxa-trim21-and-viperin-in-nasal-swabs
#9
Mohamed Yahya, Maris Rulli, Laura Toivonen, Matti Waris, Ville Peltola
Respiratory viruses frequently cause symptomatic infections in children but are often detected also in healthy children. We investigated myxovirus resistance protein A (MxA), viperin, and tripartite-motif 21 (TRIM21) mRNA indexes in nasal swabs as potential biomarkers of viral respiratory infection in children. Respiratory viruses were detected by PCR in the same swabs. Nasal MxA and viperin indexes were increased in symptomatic virus positive children. Nasal viperin index was found to be a robust marker of viral respiratory tract infection with a sensitivity of 80% and specificity of 94% in distinguishing children with symptomatic virus infections from asymptomatic virus negative children...
August 29, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28807517/trim21-and-the-function-of-antibodies-inside-cells
#10
REVIEW
David A Rhodes, David A Isenberg
Therapeutic antibodies targeting disease-associated antigens are key tools in the treatment of cancer and autoimmunity. So far, therapeutic antibodies have targeted antigens that are, or are presumed to be, extracellular. A largely overlooked property of antibodies is their functional activity inside cells. The diverse literature dealing with intracellular antibodies emerged historically from studies of the properties of some autoantibodies. The identification of tripartite motif (TRIM) 21 as an intracellular Fc receptor linking cytosolic antibody recognition to the ubiquitin proteasome system brings this research into sharper focus...
August 11, 2017: Trends in Immunology
https://www.readbyqxmd.com/read/28753623/solution-nmr-structure-of-the-trim21-b-box2-and-identification-of-residues-involved-in-its-interaction-with-the-ring-domain
#11
Amélie Wallenhammar, Madhanagopal Anandapadamanaban, Alexander Lemak, Claudio Mirabello, Patrik Lundström, Björn Wallner, Maria Sunnerhagen
Tripartite motif-containing (TRIM) proteins are defined by the sequential arrangement of RING, B-box and coiled-coil domains (RBCC), where the B-box domain is a unique feature of the TRIM protein family. TRIM21 is an E3 ubiquitin-protein ligase implicated in innate immune signaling by acting as an autoantigen and by modifying interferon regulatory factors. Here we report the three-dimensional solution structure of the TRIM21 B-box2 domain by nuclear magnetic resonance (NMR) spectroscopy. The structure of the B-box2 domain, comprising TRIM21 residues 86-130, consists of a short α-helical segment with an N-terminal short β-strand and two anti-parallel β-strands jointly found the core, and adopts a RING-like fold...
2017: PloS One
https://www.readbyqxmd.com/read/28725225/antiviral-functions-of-human-immunodeficiency-virus-type-1-hiv-1-specific-igg-antibodies-effects-of-antiretroviral-therapy-and-implications-for-therapeutic-hiv-1-vaccine-design
#12
REVIEW
Martyn A French, M Christian Tjiam, Laila N Abudulai, Sonia Fernandez
Contemporary antiretroviral therapy (ART) is effective and tolerable for long periods of time but cannot eradicate human immunodeficiency virus type 1 (HIV-1) infection by either elimination of viral reservoirs or enhancement of HIV-1-specific immune responses. Boosting "protective" HIV-1-specific immune responses by active or passive immunization will therefore be necessary to control or eradicate HIV-1 infection and is currently the topic of intense investigation. Recently reported studies conducted in HIV patients and non-human primate (NHP) models of HIV-1 infection suggest that HIV-1-specific IgG antibody responses may contribute to the control of HIV-1 infection...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28711442/association-of-ev71-3c-polymorphisms-with-clinical-severity
#13
Hsuan-Yin Ma, Chun-Yi Lu, Kuo-Chien Tsao, Hsiu-Ming Shih, Ai-Ling Cheng, Li-Min Huang, Luan-Yin Chang
OBJECTIVES: Enterovirus 71 (EV71) may cause neurological and fatal cases. EV71 3C plays an important role on viral replication and possess proteolysis activity. To delineate pathogenesis of EV71 virulence, we studied EV71 3C genetics, protease activity and correlated the results with clinical severity. METHODS: EV71 cases were collected; 3C of EV71 was sequenced and linked with clinical severity. 3C protease activity, viral replication rates of EV71 infectious clones with different 3C and 3C interaction with host proteins were analyzed...
June 28, 2017: Journal of Microbiology, Immunology, and Infection, Wei Mian Yu Gan Ran za Zhi
https://www.readbyqxmd.com/read/28701773/trim21-is-critical-for-survival-of-toxoplasma-gondii-infection-and-localises-to-gbp-positive-parasite-vacuoles
#14
Clémence Foltz, Anna Napolitano, Rabia Khan, Barbara Clough, Elizabeth M Hirst, Eva-Maria Frickel
Interferon gamma (IFNγ) is the major proinflammatory cytokine conferring resistance to the intracellular vacuolar pathogen Toxoplasma gondii by inducing the destruction of the parasitophorous vacuole (PV). We previously identified TRIM21 as an IFNγ-driven E3 ubiquitin ligase mediating the deposition of ubiquitin around pathogen inclusions. Here, we show that TRIM21 knockout mice were highly susceptible to Toxoplasma infection, exhibiting decreased levels of serum inflammatory cytokines and higher parasite burden in the peritoneum and brain...
July 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28592884/enhancement-of-th1-th17-inflammation-by-trim21-in-beh%C3%A3-et-s-disease
#15
Yuri Ahn, Ji-Hye Hwang, Zhenlong Zheng, Dongsik Bang, Do-Young Kim
The etiology of Behçet's disease (BD), a chronic, multisystemic autoinflammatory and autoimmune disease, remains unknown; however, researchers have postulated that infectious agents, such as herpes simplex virus, are significant triggering factors of BD. Tripartite motif-containing (TRIM) proteins exhibit antiviral properties, mediating antiviral defense mechanisms. The purpose of this study was to investigate TRIM21 protein expression in the monocytes of BD patients and to identify the role of TRIM21 in immune dysregulation in BD...
June 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28576352/reprint-of-alterations-of-trim21-mrna-expression-during-monocyte-maturation
#16
Marzena Lenart, Magdalena Rutkowska-Zapała, Rafał Szatanek, Kazimierz Węglarczyk, Małgorzata Stec, Karolina Bukowska-Strakova, Anna Gruca, Jarosław Czyż, Maciej Siedlar
Tripartite motif-containing protein 21 (TRIM21) play a dual role in the cytoplasm of the cells where it facilitates destruction of some antibody-coated viruses and some bacteria, and initiates synthesis of proinflammatory cytokines. Macrophages and CD16(+) monocyte subset can particularly participate in a proinflammatory response caused by viral infection, however, the molecular mechanisms underlying these processes are not fully understood. The aim of this study was to determine the level of TRIM21-mRNA expression in monocyte subsets including: classical (CD14(++)CD16(-)), intermediate (CD14(++)CD16(+)) and non-classical (CD14(+)CD16(++)) monocytes, as well as during in vitro differentiation of the isolated monocytes towards dendritic cells or macrophages...
June 2017: Immunobiology
https://www.readbyqxmd.com/read/28417151/a-review-of-the-role-and%C3%A2-clinical-utility-of-anti-ro52-trim21-in-systemic-autoimmunity
#17
REVIEW
Adrian Y S Lee
Anti-Ro52/tripartite motif-containing 21 (TRIM21) is a ubiquitous antibody found in a number of systemic autoimmune conditions including Sjögren's syndrome, systemic lupus erythematosus and systemic sclerosis, appearing in about half of these patients. Once coupled with its closely related antibody, anti-Ro60 as the anti-SSA antibody, anti-Ro52 is emerging as a unique antibody with direct pathogenic disease involvement and distinct clinical properties. As a result, recent attention has turned to this antibody and its clinical associations and utility...
August 2017: Rheumatology International
https://www.readbyqxmd.com/read/28211536/expression-profiling-of-trim-protein-family-in-thp1-derived-macrophages-following-tlr-stimulation
#18
Mei-Xiu Jiang, Xuan Hong, Bin-Bin Liao, Shui-Zhen Shi, Xiao-Fang Lai, Huai-Yu Zheng, Lin Xie, Yuan Wang, Xiao-Lei Wang, Hong-Bo Xin, Mingui Fu, Ke-Yu Deng
Activated macrophages play an important role in many inflammatory diseases including septic shock and atherosclerosis. However, the molecular mechanisms limiting macrophage activation are not completely understood. Members of the tripartite motif (TRIM) family have recently emerged as important players in innate immunity and antivirus. Here, we systematically analyzed mRNA expressions of representative TRIM molecules in human THP1-derived macrophages activated by different toll-like receptor (TLR) ligands. Twenty-nine TRIM members were highly induced (>3 fold) by one or more TLR ligands, among which 19 of them belong to TRIM C-IV subgroup...
February 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28119462/harnessing-innate-immunity-to-fight-neurodegeneration
#19
Alexandra A Mushegian
TRIM21 prevents antibody-bound tau proteins from aggregating in cells.
January 24, 2017: Science Signaling
https://www.readbyqxmd.com/read/28049840/cytosolic-fc-receptor-trim21-inhibits-seeded-tau-aggregation
#20
William A McEwan, Benjamin Falcon, Marina Vaysburd, Dean Clift, Adrian L Oblak, Bernardino Ghetti, Michel Goedert, Leo C James
Alzheimer's disease (AD) and other neurodegenerative disorders are associated with the cytoplasmic aggregation of microtubule-associated protein tau. Recent evidence supports transcellular transfer of tau misfolding (seeding) as the mechanism of spread within an affected brain, a process reminiscent of viral infection. However, whereas microbial pathogens can be recognized as nonself by immune receptors, misfolded protein assemblies evade detection, as they are host-derived. Here, we show that when misfolded tau assemblies enter the cell, they can be detected and neutralized via a danger response mediated by tau-associated antibodies and the cytosolic Fc receptor tripartite motif protein 21 (TRIM21)...
January 17, 2017: Proceedings of the National Academy of Sciences of the United States of America
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