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Immunology and Cell Biology

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https://www.readbyqxmd.com/read/28202908/silencing-c-rel-in-macrophages-dampens-th1-and-th17-immune-responses-and-alleviates-experimental-autoimmune-encephalomyelitis-in-mice
#1
Hongling Zhang, Jiacheng Bi, Huqiang Yi, Tingting Fan, Qingguo Ruan, Lintao Cai, Youhai H Chen, Xiaochun Wan
Autoimmune Th1 and Th17 responses are critical for the development of central nervous system (CNS) pathology in experimental autoimmune encephalomyelitis (EAE), an animal model for human multiple sclerosis. Although macrophages play important roles in the development of Th1 and Th17 responses, whether modulating macrophage gene transcription can diminish the Th1- and Th17 cell-induced CNS pathology is unclear. In this study, we successfully silenced the expression of the transcription factor c-Rel in macrophages of mice with EAE (including those infiltrating the CNS) using chemically modified c-Rel-specific siRNAs delivered by nanoparticles...
March 21, 2017: Immunology and Cell Biology
https://www.readbyqxmd.com/read/28303902/ms4a4a-a-novel-cell-surface-marker-for-m2-macrophages-and-plasma-cells
#2
Ratna Sanyal, Maria J Polyak, Jonathan Zuccolo, Mandip Puri, Lili Deng, Luc Roberts, Ania Zuba, Jan Storek, Joanne M Luider, Ellen M Sundberg, Adnan Mansoor, Eva Baigorri, Michael P Chu, Andrew R Belch, Linda M Pilarski, Julie P Deans
MS4A4A is a member of the membrane-spanning, 4 domain family, subfamily A (MS4A) that includes CD20 (MS4A1), FcRβ (MS4A2) and Htm4 (MS4A3). Like the first three members of this family, transcription of MS4A4A appears to be limited to hematopoietic cells. To evaluate expression of the MS4A4A protein in hematopoietic cell lineages and subsets we generated monoclonal antibodies against extracellular epitopes for use in flow cytometry. In human peripheral blood we found that MS4A4A is expressed at the plasma membrane in monocytes but not in granulocytes or lymphocytes...
March 17, 2017: Immunology and Cell Biology
https://www.readbyqxmd.com/read/28294139/imaging-to-study-solid-tumour-origin-and-progression-lessons-from-research-and-clinical-oncology
#3
REVIEW
Stefania Raimondo, Giovanni Zito
Biomedical imaging in recent decades has clarified our understanding of normal and pathological cellular processes in vivo. In particular, this approach recently provided insights into processes occurring at a molecular or genetic level rather than at the anatomical level. The evolution of this discipline by engineering have led to its integration into biomedical research to (1) increase sensitivity and resolution imaging and to (2) improve tissue and cell specificity. Currently, imaging approaches are used in three different biomedical areas: (a) identification of cellular processes in physiological and disease state, (b) in vivo single cell imaging, and (c) identification of new prognostic and therapeutical strategies...
March 15, 2017: Immunology and Cell Biology
https://www.readbyqxmd.com/read/28294138/machine-learning-applications-in-cell-image-analysis
#4
REVIEW
Andrey Kan
Machine learning refers to a set of automatic pattern recognition methods that have been successfully applied across various problem domains, including biomedical image analysis. This review focuses on machine learning applications for image analysis in light microscopy experiments with typical tasks of segmenting and tracking individual cells, and modelling of reconstructed lineage trees. After describing a typical image analysis pipeline and highlighting challenges of automatic analysis (e.g., variability in cell morphology, tracking in presence of clutters) this review gives a brief historical outlook of machine learning, followed by basic concepts and definitions required for understanding examples...
March 15, 2017: Immunology and Cell Biology
https://www.readbyqxmd.com/read/28290451/development-of-sh2-probes-and-pull-down-assays-to-detect-pathogen-induced-site-specific-tyrosine-phosphorylation-of-the-tlr-adaptor-scimp
#5
Lin Luo, Samuel J Tong, Adam A Wall, Tatiana Khromykh, Matthew J Sweet, Jennifer L Stow
Protein tyrosine phosphorylation guides many molecular interactions for cellular functions. SCIMP is a transmembrane adaptor protein (TRAP) family member that mediates selective proinflammatory cytokine responses generated by pathogen-activated Toll-like receptor (TLR) pathways in macrophages. TLR activation triggers SCIMP phosphorylation and selective phosphorylation of distinct tyrosine residues on this adaptor offers the potential for regulating or biasing inflammatory responses. To analyze site-specific phosphorylation events, we developed three probes based on the SH2 domains of known SCIMP effectors, and used them for pull-downs from macrophage extracts...
March 14, 2017: Immunology and Cell Biology
https://www.readbyqxmd.com/read/28290450/when-input-does-not-match-output-lung-resident-memory-t-cells-decay
#6
Linda M Wakim
No abstract text is available yet for this article.
March 14, 2017: Immunology and Cell Biology
https://www.readbyqxmd.com/read/28228641/evaluation-of-trained-immunity-by-%C3%AE-1-3-d-glucan-on-murine-monocytes-in-vitro-and-duration-of-response-in-vivo
#7
Pablo Garcia-Valtanen, Ruth Marian Guzman-Genuino, David L Williams, John D Hayball, Kerrilyn R Diener
The β-1, 3 (d)-glucan (β-glucan) present in the cell wall of Candida albicans induces epigenetic changes in human monocytes resulting in primed macrophages exhibiting increased cytokine responsiveness to reinfection. This phenomenon is referred to as trained immunity or innate immune memory. However, whether β-glucan can reprogramme murine monocytes in vitro or induce lasting effects in vivo has yet to be elucidated. Thus, purified murine spleen-derived monocytes were primed with β-glucan in vitro and assessed for markers of differentiation and survival...
March 14, 2017: Immunology and Cell Biology
https://www.readbyqxmd.com/read/28244489/chromosome-choice-for-initiation-of-v-d-j-recombination-is-not-governed-by-genomic-imprinting
#8
Claudia Gebert, Lauren Correia, Zhenhu Li, Howard T Petrie, Paul E Love, Karl Pfeifer
V-(D)-J recombination generates the antigen receptor diversity necessary for immune cell function, while allelic exclusion ensures that each cell expresses a single antigen receptor. V-(D)-J recombination of the Ig, Tcrb, Tcrg and Tcrd antigen receptor genes is ordered and sequential so that only one allele generates a productive rearrangement. The mechanism controlling sequential rearrangement of antigen receptor genes, in particular how only one allele is selected to initiate recombination while at least temporarily leaving the other intact, remains unresolved...
February 28, 2017: Immunology and Cell Biology
https://www.readbyqxmd.com/read/28163304/predominant-contribution-of-dgk%C3%AE-over-dgk%C3%AE-in-the-control-of-pkc-pdk-1-regulated-functions-in-t-cells
#9
Antonia Ávila-Flores, Javier Arranz-Nicolás, Elena Andrada, Denise Soutar, Isabel Mérida
Diacylglycerol kinase (DGK)-mediated consumption of the diacylglycerol (DAG) generated in response to antigen recognition is an important mechanism to limit T-cell function. Targeting DGK activity presents new opportunities for therapeutic manipulation of the immune response, but assessment of individual DGK functions is complex. T cells express two DGK isoforms, DGKα and DGKζ, and there are no isoform-specific inhibitors. Here we used short interfering RNA-mediated gene silencing in human T cells and DGKα- and DGKζ-deficient mice to define DGK isoform-specific regulation of key signaling pathways during T-cell activation...
February 28, 2017: Immunology and Cell Biology
https://www.readbyqxmd.com/read/28220810/dengue-virus-ns1-protein-activates-immune-cells-via-tlr4-but-not-tlr2-or-tlr6
#10
Naphak Modhiran, Daniel Watterson, Antje Blumenthal, Alan G Baxter, Paul R Young, Katryn J Stacey
The secreted hexameric form of the dengue virus (DENV) non-structural protein 1 (NS1) has recently been shown to elicit inflammatory cytokine release and disrupt endothelial cell monolayer integrity. This suggests that circulating NS1 contributes to the vascular leak that plays a major role in the pathology of dengue haemorrhagic fever and shock. Pathways activated by NS1 are thus of great interest as potential therapeutic targets. Recent works have separately implicated both toll-like receptor 4 (TLR4) and the TLR2/6 heterodimer in immune cell activation by NS1...
February 21, 2017: Immunology and Cell Biology
https://www.readbyqxmd.com/read/28174424/targeting-a2-adenosine-receptors-in-cancer
#11
REVIEW
David Allard, Martin Turcotte, John Stagg
Tumor cells use various ways to evade anti-tumor immune responses. Adenosine, a potent immunosuppressive metabolite, is often found elevated in the extracellular tumor microenvironment. Therefore, targeting adenosine-generating enzymes (CD39 and CD73) or adenosine receptors has emerged as a novel means to stimulate anti-tumor immunity. In particular, the A2 (A2a and A2b) adenosine receptors exhibit similar immunosuppressive and pro-angiogenic functions, yet have distinct biological roles in cancer. In this review, we describe the common and distinct biological consequences of A2a and A2b adenosine receptor signaling in cancer...
February 21, 2017: Immunology and Cell Biology
https://www.readbyqxmd.com/read/28138156/antibody-dependent-cell-cytotoxicity-immunotherapy-strategies-enhancing-effector-nk-cells
#12
REVIEW
Maria Carmen Ochoa, Luna Minute, Inmaculada Rodriguez, Saray Garasa, Elisabeth Perez-Ruiz, Susana Inogés, Ignacio Melero, Pedro Berraondo
Antibody-dependent cellular cytotoxicity (ADCC) is a set of mechanisms that target cells coated with IgG antibodies of the proper subclasses (IgG1 in the human) to be the prey of cell-to-cell cytolysis executed by immune cells expressing FcRIIIA (CD16A). These effectors include not only natural killer (NK) cells but also other CD16(+) subsets such as monocyte/macrophages, NKT cells or γδ T cells. In cancer therapy, ADCC is exploited by antibodies that selectively recognize proteins on the surface of malignant cells...
February 21, 2017: Immunology and Cell Biology
https://www.readbyqxmd.com/read/28174425/multiple-approaches-to-immunotherapy-the-new-pillar-of-cancer-treatment
#13
EDITORIAL
Mark J Smyth
Immunology and Cell Biology accepted article preview online, 08 February 2017. doi:10.1038/icb.2017.9.
February 8, 2017: Immunology and Cell Biology
https://www.readbyqxmd.com/read/28169287/il-10-producing-st2-expressing-foxp3-t-cells-in-multiple-sclerosis-brain-lesions
#14
Stephanie Elizabeth Johanna Zandee, Richard Anthony O'Connor, Iris Mair, Melanie Dawn Leech, Anna Williams, Stephen Mark Anderton
CD4(+)Foxp3(+) T regulatory (Treg) cells provide a key defence against inflammatory disease, but also have an ability to produce pro-inflammatory cytokines. The evidence for these two possibilities in multiple sclerosis (MS) is controversial. However, this has largely been based on studies of circulating Treg cells derived from peripheral blood, rather than the central nervous system. We show that Foxp3(+) cells in the brains of MS patients predominantly produce interleukin-10 (IL-10) and show high expression of the IL-33 receptor ST2 (associated with potent Treg function), indicating that Treg in the inflamed brain maintain their suppressive function...
February 7, 2017: Immunology and Cell Biology
https://www.readbyqxmd.com/read/28108746/myeloid-derived-suppressor-cells-can-be-efficiently-generated-from-human-hematopoietic-progenitors-and-peripheral-blood-monocytes
#15
Sílvia Casacuberta-Serra, Marta Parés, Arantxa Golbano, Elisabet Coves, Carmen Espejo, Jordi Barquinero
Myeloid-derived suppressor cells (MDSCs) play an important role in controlling inflammation. As such, they are both a therapeutic target and, based on the administration of ex-vivo-generated MDSCs, a therapeutic tool. However, there are relatively few reports describing methods to generate human MDSCs, and most of them rely on cells obtained from peripheral blood monocytes. We investigated alternative approaches to the generation of MDSCs from hematopoietic progenitors and monocytes. Purified CD34(+) hematopoietic progenitors from apheresis products and CD14(+) cells isolated from buffy coats were cultured in the presence of different combinations of cytokines...
January 21, 2017: Immunology and Cell Biology
https://www.readbyqxmd.com/read/27999433/insane-in-the-membrane-a-structural-perspective-of-mlkl-function-in-necroptosis
#16
REVIEW
Emma J Petrie, Joanne M Hildebrand, James M Murphy
Necroptosis (or 'programmed necrosis') is a caspase-independent cell death pathway that operates downstream of death receptors, including Tumour Necrosis Factor Receptor-1 (TNFR1), and the Toll-like receptors, TLR3 and TLR4. Owing to its immunogenicity, necroptosis has been attributed roles in the pathogenesis of several diseases, including inflammatory bowel disease and the tissue damage arising from ischaemic-reperfusion injuries. Only over the past 7 years has the core machinery of this pathway, the receptor-interacting protein kinase-3 (RIPK3) and the pseudokinase, Mixed Lineage Kinase domain-Like (MLKL), been defined...
January 17, 2017: Immunology and Cell Biology
https://www.readbyqxmd.com/read/27922620/relevance-of-necroptosis-in-cancer
#17
REVIEW
Najoua Lalaoui, Gabriela Brumatti
Resistance to caspase-dependent apoptosis is often responsible for treatment failures in cancer. Finding novel therapeutic strategies that can activate alternative cell death programs appears to be appealing. Necroptosis is a form of programmed necrosis that occurs under caspase-deficient conditions. This alternative form of cell death has recently emerged as a potential anticancer therapy that could overcome apoptosis resistance. A growing understanding of the molecular events triggering necroptosis helped to examine its implication in cancer development and to define new therapeutic strategies...
January 17, 2017: Immunology and Cell Biology
https://www.readbyqxmd.com/read/28074060/s100a8-a9-and-s100a9-reduce-acute-lung-injury
#18
Yuka Hiroshima, Kenneth Hsu, Nicodemus Tedla, Sze Wing Wong, Sharron Chow, Naomi Kawaguchi, Carolyn L Geczy
S100A8 and S100A9 are myeloid cell-derived proteins that are elevated in several types of inflammatory lung disorders. Pro- and anti-inflammatory properties are reported and these proteins are proposed to activate TLR4. S100A8 and S100A9 can function separately, likely through distinct receptors but a systematic comparison of their effects in vivo are limited. Here we assess inflammation in murine lung following S100A9 and S100A8/A9 inhalation. Unlike S100A8, S100A9 promoted mild neutrophil and lymphocyte influx, possibly mediated in part, by increased mast cell degranulation and selective upregulation of some chemokine genes, particularly CXCL-10...
January 11, 2017: Immunology and Cell Biology
https://www.readbyqxmd.com/read/28045025/interferon-epsilon-promotes-hiv-restriction-at-multiple-steps-of-viral-replication
#19
Albert Garcia-Minambres, Sahar G Eid, Niamh E Mangan, Corinna Pade, San S Lim, Antony Y Matthews, Nicole A de Weerd, Paul J Hertzog, Johnson Mak
Interferon epsilon (IFNɛ) is a type I IFN that is expressed constitutively in the female reproductive tract (FRT), and contributes to protection in models of sexually transmitted infections. Using multiple cell systems, including reporter cell lines and activated peripheral blood lymphocytes (PBLs), we show that recombinant IFNɛ impairs HIV infection at stage(s) post HIV entry and up to the translation of viral proteins. Consistent with this, IFNɛ upregulated a number of host cell restriction factors that block HIV at these stages of the replication cycle...
January 3, 2017: Immunology and Cell Biology
https://www.readbyqxmd.com/read/27974746/role-of-fc-fc%C3%AE-r-interactions-in-the-antitumor-activity-of-therapeutic-antibodies
#20
REVIEW
Bryan C Barnhart, Michael Quigley
The use of antibody therapy for cancer has steadily increased in recent years and has become standard treatment for numerous tumor types. It is now appreciated that the clinical activity of these antibodies relies upon their specific interactions with Fc receptors in addition to the well-studied target-binding region. The interactions mediated by antibody Fc domains can strongly affect the functional outcome of antibody therapy. The Fc portion of an antibody defines its interaction with numerous immune cells and has become an intense area of research as selecting the optimal Fc can greatly enhance the activity as well as mechanism of action of therapeutic antibodies...
January 3, 2017: Immunology and Cell Biology
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