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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...
November 18, 2016: 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
Keunok Jung, Su-Kil Seo, Inhak Choi
VSIG4 acts as a co-inhibitory ligand to negatively regulate T cell proliferation and cytokine production, and its expression is restricted to macrophages. We hypothesized that endogenous VSIG4 impairs helper T cell functions and then inhibits the subsequent antibody response. Isotype switching of ovalbumin (OVA)-specific antibody subclasses to IgG1, IgG2a, IgG2b, and IgG3 was enhanced in OVA-immunized VSIG4 knockout (KO) mice. 2,4,6-Trinitrophenyl hapten (TNP) - Keyhole Limpet Hemocyanin (KLH)-primed B cells cocultured with OVA-primed CD4(+) T cells from OVA-immunized VSIG4 KO mice in the presence of TNP-OVA showed enhanced isotype switching to IgG subclasses compared to those cocultured with cells isolated from OVA-immunized wild-type (WT) mice...
June 2015: Immunology Letters
Thomas G di Salvo, Kai-Chien Yang, Evan Brittain, Tarek Absi, Simon Maltais, Anna Hemnes
BACKGROUND: Right ventricular (RV) dysfunction contributes to mortality in chronic heart failure (HF). However, the molecular mechanisms of RV failure remain poorly understood, and RV myocardial biomarkers have yet to be developed. METHODS AND RESULTS: We performed RNA sequencing (RNA-seq) on 22 explanted human HF RVs and 5 unused donor human heart RVs (DON RV) and compared results to those recently reported from 16 explanted human LVs We used Bowtie-Tophat for transcript alignment and transcriptome assembly, DESeq for identification of differentially expressed genes (DEGs) and Ingenuity for exploration of gene ontologies...
May 2015: Journal of Cardiac Failure
Fang Zheng, Nick Devoogdt, Amanda Sparkes, Yannick Morias, Chloé Abels, Benoit Stijlemans, Tony Lahoutte, Serge Muyldermans, Patrick De Baetselier, Steve Schoonooghe, Alain Beschin, Geert Raes
Kupffer cells (KCs) are liver resident macrophages which are important for tissue homeostasis and have been implicated in immunogenic, tolerogenic and pathogenic immune reactions depending on the insult. These cells and the biomarkers they express thus represent interesting in vivo sensors for monitoring liver inflammation. In the current study, we explored whether KCs can be monitored non-invasively using single-photon-emission computed tomography (SPECT) with (99m)Tc labeled nanobodies (Nbs) targeting selected biomarkers...
February 2015: Immunobiology
Yunmei Liao, Sheng Guo, Yongwen Chen, Dayan Cao, Huan Xu, Chengying Yang, Lei Fei, Bing Ni, Zhihua Ruan
Tumor-associated macrophages are a prominent component of lung cancer stroma and contribute to tumor progression. The protein V-set and Ig domain-containing 4 (VSIG4), a novel B7 family-related macrophage protein that has the capacity to inhibit T-cell activation, has a potential role in the development of lung cancer. In this study, 10 human non-small-cell lung cancer specimens were collected and immunohistochemically analyzed for VSIG4 expression. Results showed massive VSIG4(+) cell infiltration throughout the samples...
July 2014: Laboratory Investigation; a Journal of Technical Methods and Pathology
Lori A Sturtz, Brenda Deyarmin, Ryan van Laar, William Yarina, Craig D Shriver, Rachel E Ellsworth
Long thought to function only as an inert energy storage depot, the role of adipose tissue in breast tumorigenesis has been largely ignored. In light of increasing rates of obesity and use of breast conserving therapy and autologous fat grafting, improved understanding of the role of adipose tissue in tumor etiology is crucial. Thus, adipose tissue adjacent to and distant from invasive breast tumors (n = 20), or adjacent to non-malignant diagnoses (n = 20) was laser microdissected from post-menopausal women...
April 1, 2014: Adipocyte
Yan Li, Yi-Qin Wang, Dai-Hong Wang, Wei-Ping Hou, Ying Zhang, Ming Li, Fu-Rong Li, Jiao Mu, Xiang Du, Fang Pang, Fa-Huan Yuan
BACKGROUND: Activation and infiltration of T cells and macrophages are key features of renal tubulointerstitial injury. The costimulatory molecule V-set and immunoglobulin domain-containing protein-4 (VSIG4), which is exclusively expressed on macrophages, is capable of inhibiting the T cell response. However, it is unclear whether VSIG4 is involved in renal tubulointerstitial injury. This study was designed to investigate the role of VSIG4 in renal tubulointerstitial injury and the related T cell infiltration...
February 2014: Journal of Nephrology
Julien Textoris, Delphine Ivorra, Amira Ben Amara, Florence Sabatier, Jean-Pierre Ménard, Hélène Heckenroth, Florence Bretelle, Jean-Louis Mege
Preeclampsia is a placental disease characterized by hypertension and proteinuria in pregnant women, and it is associated with a high maternal and neonatal morbidity. However, circulating biomarkers that are able to predict the prognosis of preeclampsia are lacking. Thirty-eight women were included in the current study. They consisted of 19 patients with preeclampsia (13 with severe preeclampsia and 6 with non-severe preeclampsia) and 19 gestational age-matched women with normal pregnancies as controls. We measured circulating factors that are associated with the coagulation pathway (including fibrinogen, fibronectin, factor VIII, antithrombin, protein S and protein C), endothelial activation (such as soluble endoglin and CD146), and the release of total and platelet-derived microparticles...
2013: PloS One
Tinnakorn Chaiworapongsa, Roberto Romero, Amy Whitten, Adi L Tarca, Gaurav Bhatti, Sorin Draghici, Piya Chaemsaithong, Jezid Miranda, Sonia S Hassan
OBJECTIVE: Preeclampsia (PE) can be sub-divided into early- and late-onset phenotypes. The pathogenesis of these two phenotypes has not been elucidated. To gain insight into the mechanisms of disease, the transcriptional profiles of whole blood from women with early- and late-onset PE were examined. METHODS: A cross-sectional study was conducted to include women with: i) early-onset PE (diagnosed prior to 34 weeks, n=25); ii) late-onset PE (after 34 weeks, n=47); and iii) uncomplicated pregnancy (n=61)...
September 1, 2013: Journal of Perinatal Medicine
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