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Menno van Lookeren Campagne, Admar Verschoor
Rapid elimination of microbes from the bloodstream, along with the ability to mount an adaptive immune response, are essential for optimal host-defense. Kupffer cells are strategically positioned in the liver sinusoids and efficiently capture circulating microbes from the hepatic artery and portal vein, thus preventing bacterial dissemination. In vivo and in vitro studies have probed how complement receptor of the immunoglobulin superfamily (CRIg), also referred to as Z39Ig and V-set and Ig domain-containing 4 (VSIG4), acts as a critical player in pathogen recognition and clearance...
March 21, 2018: Seminars in Immunology
Sam J L van der Tuin, Zhuang Li, Jimmy F P Berbée, Inge Verkouter, Linda E Ringnalda, Annette E Neele, Jan B van Klinken, Sander S Rensen, Jingyuan Fu, Menno P J de Winther, Albert K Groen, Patrick C N Rensen, Ko Willems van Dijk, Yanan Wang
BACKGROUND: Lipopolysaccharide (LPS) decreases hepatic CETP (cholesteryl ester transfer protein) expression albeit that the underlying mechanism is disputed. We recently showed that plasma CETP is mainly derived from Kupffer cells (KCs). In this study, we investigated the role of KC subsets in the mechanism by which LPS reduces CETP expression. METHODS AND RESULTS: In CETP-transgenic mice, LPS markedly decreased hepatic CETP expression and plasma CETP concentration without affecting hepatic macrophage number...
March 10, 2018: Journal of the American Heart Association
Wonhwa Shin, Youkyoung Jeon, Inhak Choi, Yeon-Jeong Kim
Oral tolerance can prevent unnecessary immune responses against dietary antigens. Members of the B7 protein family play critical roles in the positive and/or negative regulation of T cell responses to interactions between APCs and T cells. V-set and Ig domain-containing 4 (VSIG4), a B7-related co-signaling molecule, has been known to act as a co-inhibitory ligand and may be critical in establishing immune tolerance. Therefore, we investigated the regulation of VSIG4 signaling in a food allergy and experimental oral tolerance murine models...
December 13, 2017: European Journal of Immunology
Jialin Li, Bo Diao, Sheng Guo, Xiaoyong Huang, Chengying Yang, Zeqing Feng, Weiming Yan, Qin Ning, Lixin Zheng, Yongwen Chen, Yuzhang Wu
Exacerbation of macrophage-mediated inflammation contributes to pathogenesis of various inflammatory diseases, but the immunometabolic programs underlying regulation of macrophage activation are unclear. Here we show that V-set immunoglobulin-domain-containing 4 (VSIG4), a B7 family-related protein that is expressed by resting macrophages, inhibits macrophage activation in response to lipopolysaccharide. Vsig4-/- mice are susceptible to high-fat diet-caused obesity and murine hepatitis virus strain-3 (MHV-3)-induced fulminant hepatitis due to excessive macrophage-dependent inflammation...
November 6, 2017: Nature Communications
Jin Roh, Youkyoung Jeon, A-Neum Lee, Sang Min Lee, YeonMee Kim, Chang Ohk Sung, Chan-Jeoung Park, Jung Yong Hong, Dok Hyun Yoon, Cheolwon Suh, Jooryung Huh, Inhak Choi, Chan-Sik Park
Multiple myeloma (MM) remains as an incurable disease, despite recent substantial improvements in treatment. Therefore, development of novel biomarkers for risk stratification and new therapeutic targets are imperative. One of the emerging treatments for MM is the immune checkpoint blockades. V-set Ig domain-containing 4 (VSIG4) is a lately studied B7-related immune checkpoint modulator. We assessed the VSIG4 expression in patients with MM and its prognostic impact. We analyzed 81 bone marrow and 66 extramedullary biopsy samples of MM patients using immunohistochemistry...
August 29, 2017: Oncotarget
Seung-Mi Kim, Se Won Oh, Sang Hyun Park, Dae Young Hur, Seung-Woo Hong, Sang Youb Han
The epithelial to mesenchymal transition (EMT), a hallmark of chronic kidney disease, is a key event in the conversion from tubular epithelial cells to myofibroblasts in renal fibrosis. Epstein-Barr virus (EBV) is a γ-herpes oncovirus associated with chronic kidney disease. However, the relationship between EBV and the EMT process in renal tubular epithelial cells is not well understood. Among EBV-latent genes, EBV-encoded latent membrane protein 1 (LMP1) induces EMT by regulating a variety of molecules in EBV-induced oncogenic transformation...
October 21, 2017: Biochemical and Biophysical Research Communications
Kim M Summers, David A Hume
The FANTOM5 consortium used cap analysis of gene expression (CAGE) to analyze the time course of gene expression over development from 11 days postcoitum (dpc) to adult in 16 developing organs and the whole body of the mouse. Every tissue in the body contains a large number of resident macrophages that initially infiltrate the embryo from the yolk sac. These cells contribute to organogenesis, and their functions diversify during development as they acquire tissue-specific adaptations. In each of the FANTOM5 time courses, the expression of known macrophage-specific genes, including CSF1 receptor (Csf1r), epidermal growth factor-like module-containing mucin-like hormone receptor-like 1 (Emr1), and mer receptor tyrosine kinase (Mertk), was readily detectable and increased with time...
October 2017: Journal of Leukocyte Biology
Jung Mi Byun, Dae Hoon Jeong, In Hak Choi, Dae Sim Lee, Mi Seon Kang, Keun Ok Jung, You Kyung Jeon, Young Nam Kim, Eun Jung Jung, Kyung Bok Lee, Moon Su Sung, Ki Tae Kim
OBJECTIVES: The protein V-set and Ig domain-containing 4 (VSIG4), a novel B7 family-related macrophage protein with the capacity to inhibit T-cell activation, has a potential role in cancer. Here we suggest its possibility as a therapeutic target and prognostic biomarker of ovarian cancer. METHODS: Between January 2011 and June 2015, tumor tissues and peripheral blood samples were obtained during surgery from 10 patients with benign ovarian tumors and 22 patients with ovarian cancers...
June 2017: International Journal of Gynecological Cancer
Yurong Wen, Zhenlin Ouyang, Steve Schoonooghe, Siyu Luo, Patrick De Baetselier, Wuyuan Lu, Serge Muyldermans, Geert Raes, Fang Zheng
Vsig4 is a recently identified immune regulatory protein related to the B7 family with dual functionality: a negative regulator of T cell activation and a receptor for the complement components C3b and C3c. Here we present a structural evaluation of a nanobody, Nb119, against the extracellular IgV domain protein of both mouse and human recombinant Vsig4, which have a high degree of sequence identity. Although mouse and human Vsig4 bind to Nb119 with a 250 times difference in dissociation constants, the interaction results in a highly identical assembly with a RMSD of 0...
June 2017: Immunobiology
Michael L Dustin
Myeloid cells make extensive use of the complement system in the context of recruitment, phagocytosis, and other effector functions. There are several types of complement receptors on myeloid cells, including G protein-coupled receptors for localizing the source of complement activation, and three sets of type I transmembrane proteins that link complement to phagocytosis: complement receptor 1, having an extracellular domain with tandem complement regulatory repeats; complement receptors 3 and 4, which are integrin family receptors comprising heterodimers of type I transmembrane subunits; and VSIG4, a member of the Ig superfamily...
November 2016: Microbiology Spectrum
Jin Roh, Keunok Jung, A-Neum Lee, Yeon Mee Kim, Jooryung Huh, Inhak Choi, Chan-Sik Park
No abstract text is available yet for this article.
February 2016: Pathology
Xin-Hua Zhang, Yun Qian, Zheng Li, Ning-Ning Zhang, Yun-Jie Xie
Epithelial-mesenchymal transition (EMT) and stem-like glioma cells display hallmark therapeutic resistance. Understanding of the mechanisms underlying these properties will be vital for the development of effective therapies. In this study, we found that VSIG4 protein is upregulated in glioblastoma. Overexpressing VSIG4 induced EMT and significantly promoted invasion and migration in glioblastoma U-87MG cells. Moreover, we showed that its overexpression promoted formation of glioma stem cell phenotypes in U-87MG cells...
November 2016: Oncology Reports
Shalini Vellasamy, Chih Kong Tong, Nur Atiqah Azhar, Radha Kodiappan, Soon Choy Chan, Abhi Veerakumarasivam, Rajesh Ramasamy
BACKGROUND AIMS: Mesenchymal stromal cells (MSCs) have been identified as pan-immunosuppressant in various in vitro and in vivo inflammatory models. Although the immunosuppressive activity of MSCs has been explored in various contexts, the precise molecular signaling pathways that govern inhibitory functions remain poorly elucidated. METHODS: By using a microarray-based global gene expression profiling system, this study aimed to decipher the underlying molecular pathways that may mediate the immunosuppressive activity of umbilical cord-derived MSCs (UC-MSCs) on activated T cells...
October 2016: Cytotherapy
Kwang H Kim, Beom K Choi, Young H Kim, Chungyong Han, Ho S Oh, Don G Lee, Byoung S Kwon
VSIG4/CRIg (V-set and immunoglobulin domain containing 4) is a transmembrane receptor of the immunoglobulin superfamily that is expressed specifically on macrophages and mature dendritic cells. VSIG4 signaling accelerates phagocytosis of C3-opsonized bacteria, thereby efficiently clearing pathogens within macrophages. We found that VSIG4 signaling triggered by C3-opsonized Listeria (opLM) or by agonistic anti-VSIG4 monoclonal antibody (mAb) induced macrophages to form autophagosomes. VSIG4-induced autophagosomes were selectively colocalized with the intracellular LM while starvation-induced autophagosomes were not...
September 2016: Autophagy
Fang Zheng, Amanda Sparkes, Patrick De Baetselier, Steve Schoonooghe, Benoit Stijlemans, Serge Muyldermans, Véronique Flamand, Jo A Van Ginderachter, Nick Devoogdt, Geert Raes, Alain Beschin
PURPOSE: Kupffer cells (KCs), the liver resident macrophages, are important mediators of tissue homeostasis and pathogen clearance. However, depending on the inflammatory stimuli, KCs have been involved in divergent hepato-protective or hepato-destructive immune responses. The versatility of KCs in response to environmental triggers, in combination with the specific biomarkers they express, make these macrophages attractive in vivo targets for non-invasive monitoring of liver inflammation or pathogenicity...
February 2017: Molecular Imaging and Biology: MIB: the Official Publication of the Academy of Molecular Imaging
M Port, F Herodin, M Valente, M Drouet, A Lamkowski, M Majewski, M Abend
We implemented a two-stage study to predict late occurring hematologic acute radiation syndrome (HARS) in a baboon model based on gene expression changes measured in peripheral blood within the first two days after irradiation. Eighteen baboons were irradiated to simulate different patterns of partial-body and total-body exposure, which corresponded to an equivalent dose of 2.5 or 5 Gy. According to changes in blood cell counts the surviving baboons (n = 17) exhibited mild (H1-2, n = 4) or more severe (H2-3, n = 13) HARS...
July 2016: Radiation Research
Annabelle Grace Small, Marwah Al-Baghdadi, Alex Quach, Charles Hii, Antonio Ferrante
The B7 family-related protein, V-set and Ig domain (VSIG4) / Z39Ig / complement receptor immunoglobulin (CRIg), is a new player in the regulation of immunity to infection and inflammation. The unique features of this receptor as compared with classical complement receptors, CR3 and CR4, have heralded the emergence of new concepts in the regulation of innate and adaptive immunity. Its selective expression in tissue macrophages and dendritic cells has been considered of importance in host defence and in maintaining tolerance against self-antigens...
2016: Swiss Medical Weekly
Caiye Zhu, Hongying Fan, Zehu Yuan, Shijin Hu, Li Zhang, Caihong Wei, Qin Zhang, Fuping Zhao, Lixin Du
Artificial selection has played a critical role in animal breeding. Detection of artificial selection footprints in genomic regions can provide insights for understanding the function of specific phenotypic traits and better guide animal breeding. To more fully understand the relationship between genomic composition and phenotypic diversity arising from breed development, a genome-wide scan was conducted using an OvineSNP50 BeadChip and integrated haplotype score and fixation index analyses to detect selection signatures on the X chromosome in three sheep breeds...
2015: International Journal of Molecular Sciences
Tao Xu, Ying Jiang, Yong Yan, Hongxiang Wang, Chengyin Lu, Hanchong Xu, Weiqing Li, Da Fu, Yicheng Lu, Juxiang Chen
The high-grade glioma (HGG) remains as the greatest challenge for cancer management worldwide. Identification of novel therapeutics and diagnostic method is in urgent need. The V-set and immunoglobulin domain-containing protein 4 (VSIG4) is a complement receptor for C3b/iC3b and inhibits cytotoxic T lymphocytes activation, which may play important roles in glioma oncogenesis. In this study, we performed immunohistochemistry in tissue microarray to determine the expression of VSIG4 in malignant glioma and normal brain...
2015: American Journal of Translational Research
Priyanka Sharma, Anju Bansal, Prakash Chand Sharma
Individuals subjected to hypobaric hypoxia at high altitudes may exhibit differential physiological responses in terms of susceptibility and tolerance to the development of hypoxia-related disorders. We studied early-phase gene expression in the lungs of Sprague-Dawley rats exhibiting such differential physiological responses after exposure to acute hypobaric hypoxia for 1 h at a simulated altitude of 9144 m. RNA-seq transcriptome profiling of lung tissues revealed differential gene expression in tolerant and susceptible groups, subsequently validated by qRT-PCR for ten selected differentially expressed genes...
December 2015: Molecular Genetics and Genomics: MGG
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