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Immunological synapse

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https://www.readbyqxmd.com/read/28928741/cxcl12-mediates-aberrant-costimulation-of-b-lymphocytes-in-warts-hypogammaglobulinemia-infections-myelokathexis-immunodeficiency
#1
Giuliana Roselli, Elisa Martini, Vassilios Lougaris, Raffaele Badolato, Antonella Viola, Marinos Kallikourdis
The Warts, Hypogammaglobulinemia, Infections, Myelokathexis (WHIM) syndrome is an immunodeficiency caused by mutations in chemokine receptor CXCR4. WHIM patient adaptive immunity defects remain largely unexplained. We have previously shown that WHIM-mutant T cells form unstable immunological synapses, affecting T cell activation. Here, we show that, in WHIM patients and WHIM CXCR4 knock-in mice, B cells are more apoptosis prone. Intriguingly, WHIM-mutant B cells were also characterized by spontaneous activation...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28900679/ctla-4-an-essential-immune-checkpoint-for-t-cell-activation
#2
Shunsuke Chikuma
The response of peripheral T lymphocytes (T cell) is controlled by multiple checkpoints to avoid unwanted activation against self-tissues. Two opposing costimulatory receptors, CD28 and CTLA-4, on T cells bind to the same ligands (CD80 and CD86) on antigen-presenting cells (APCs), and provide positive and negative feedback for T-cell activation, respectively. Early studies suggested that CTLA-4 is induced on activated T cells and binds to CD80/CD86 with much stronger affinity than CD28, providing a competitive inhibition...
September 13, 2017: Current Topics in Microbiology and Immunology
https://www.readbyqxmd.com/read/28894104/nfatc1-controls-the-cytotoxicity-of-cd8-t-cells
#3
Stefan Klein-Hessling, Khalid Muhammad, Matthias Klein, Tobias Pusch, Ronald Rudolf, Jessica Flöter, Musga Qureischi, Andreas Beilhack, Martin Vaeth, Carsten Kummerow, Christian Backes, Rouven Schoppmeyer, Ulrike Hahn, Markus Hoth, Tobias Bopp, Friederike Berberich-Siebelt, Amiya Patra, Andris Avots, Nora Müller, Almut Schulze, Edgar Serfling
Cytotoxic T lymphocytes are effector CD8(+) T cells that eradicate infected and malignant cells. Here we show that the transcription factor NFATc1 controls the cytotoxicity of mouse cytotoxic T lymphocytes. Activation of Nfatc1 (-/-) cytotoxic T lymphocytes showed a defective cytoskeleton organization and recruitment of cytosolic organelles to immunological synapses. These cells have reduced cytotoxicity against tumor cells, and mice with NFATc1-deficient T cells are defective in controlling Listeria infection...
September 11, 2017: Nature Communications
https://www.readbyqxmd.com/read/28865025/role-of-drebrin-at-the-immunological-synapse
#4
Vera Rocha-Perugini, Mónica Gordon-Alonso, Francisco Sánchez-Madrid
Although drebrin was first described in neurons, it is also expressed in cells of the immune system, such as T lymphocytes and mast cells. Another member of the drebrin family of proteins, mammalian actin-binding protein 1 (mAbp-1) is more widely expressed and plays important roles in the function of macrophages, polymorphonuclear neutrophils, and B lymphocytes. We will briefly discuss on the function of mAbp-1 and drebrin in immune cells with emphasis on T cells. Specifically, drebrin enables the immune responses of CD4(+) T lymphocytes...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28865011/general-introduction-to-drebrin
#5
Tomoaki Shirao, Yuko Sekino
Drebrin was first discovered by our group as "developmentally regulated brain protein" from the chicken optic tectum. Drebrin is an actin-binding protein, which is classified into two major isoforms produced by alternative splicing from a single DBN1 gene. The isoform predominantly expressed in the adult brain (drebrin A) is neuron specific, containing a neuron-specific sequence (Ins2) in the middle of the molecule. Drebrin A is highly concentrated in dendritic spines, and its accumulation level is regulated by synaptic activity...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28863820/sterol-regulation-of-voltage-gated-k-channels
#6
Andras Balajthy, Peter Hajdu, Gyorgy Panyi, Zoltan Varga
Cholesterol is an essential lipid building block of the cellular plasma membrane. In addition to its structural role, it regulates the fluidity and raft structure of the membrane and influences the course of numerous membrane-linked signaling pathways and the function of transmembrane proteins, including ion channels. This is supported by a vast body of scientific data, which demonstrates the modulation of ion channels with a great variety of ion selectivity, gating, and tissue distribution by changes in membrane cholesterol...
2017: Current Topics in Membranes
https://www.readbyqxmd.com/read/28851742/platelets-in-wiskott-aldrich-syndrome-victims-or-executioners
#7
REVIEW
Lucia Sereni, Maria Carmina Castiello, Anna Villa
Microthrombocytopenia is the clinical hallmark of WAS, a rare X-linked immunodeficiency that is characterized by eczema, autoimmunity, and cancer susceptibility. This disease is caused by mutations in the WAS gene, which is expressed in hematopoietic cells and regulates actin cytoskeleton remodeling thereby modulating various cellular functions, including motility, immunologic synapse assembly, and signaling. Despite extensive studies that have provided great insight into the relevance of this molecule to innate and cellular immunity, the exact mechanisms of microthrombocytopenia in WAS are still unknown...
August 29, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28843649/change-in-nomenclature-for-the-immunologic-synapse-from-troxis-necrosis-to-trogocytosis
#8
Samuel W French
The immunologic synapse mechanism of liver necrosis was termed Troxis Necrosis meaning "nibbling". (Wang MX et al. and French SW. Exp Mol Pathol 2001, 71: 137-146). This mechanism of liver injury was first named "Piecemeal Necrosis" by Hans Popper. It is involved in autoimmune hepatitis, HCV, HBV, primary biliary cirrhosis and steatohepatitis. This process involves the T cell receptor (TCR) which binds to the hepatocyte antigen presenting major histocompatibility complex (MHC) on the hepatocytic plasma membrane which quickly leads to the removal of the complex from the liver and uptake by the CD4 lymphocyte...
August 24, 2017: Experimental and Molecular Pathology
https://www.readbyqxmd.com/read/28835459/termination-of-the-activating-nk-cell-immunological-synapse-is-an-active-and-regulated-process
#9
Petra Netter, Moritz Anft, Carsten Watzl
Cellular cytotoxicity is essential for the elimination of virus-infected and cancerous cells by NK cells. It requires a direct cellular contact through the establishment of an immunological synapse (IS) between the NK cell and the target cell. In this article, we show that not only the establishment of the IS, but also its maintenance is a highly regulated process. Ongoing receptor-proximal signaling events from activating NK cell receptors and actin dynamics were necessary to maintain a stable contact in an energy-dependent fashion, even after the IS was formed successfully...
August 23, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28833060/tcr-signalling-network-organization-at-the-immunological-synapses-of-murine-regulatory-t-cells
#10
Marco van Ham, René Teich, Lars Philipsen, Jana Niemz, Nicole Amsberg, Josef Wissing, Manfred Nimtz, Lothar Gröbe, Stefanie Kliche, Nadine Thiel, Frank Klawonn, Mario Hubo, Helmut Jonuleit, Peter Reichardt, Andreas J Müller, Jochen Huehn, Lothar Jänsch
Regulatory T (Treg) cells require T-cell receptor (TCR) signalling to exert their immunosuppressive activity, but the precise organization of the TCR signalling network compared to conventional T (Tconv) cells remains elusive. By using accurate mass spectrometry and multi-epitope ligand cartography (MELC) we characterized TCR signalling and recruitment of TCR signalling components to the immunological synapse (IS) in Treg cells and Tconv cells. With the exception of Themis which we detected in lower amounts in Treg cells, other major TCR signalling components were found equally abundant, however, their phosphorylation-status notably discriminates Treg cells from Tconv cells...
August 17, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28822075/recycling-endosomes-in-human-cytotoxic-t-lymphocytes-constitute-an-auxiliary-intracellular-trafficking-pathway-for-newly-synthesized-perforin
#11
Kelsey Lesteberg, Jordan Orange, George Makedonas
Although cytotoxic T lymphocytes (CTLs) store perforin within cytoplasmic secretory granules for immediate use, perforin is synthesized anew within hours of TCR stimulation. Previously, we observed new perforin protein at an immunologic synapse independent of secretory lysosomes; herein, we aimed to determine how new perforin transits to the synapse if not via lytic granules. We analyzed antigen-specific human CTLs via imaging flow cytometry and high-resolution confocal microscopy, with attention to intracellular trafficking components and new perforin...
August 18, 2017: Immunologic Research
https://www.readbyqxmd.com/read/28817635/contractile-actomyosin-arcs-promote-the-activation-of-primary-mouse-t-cells-in-a-ligand-dependent-manner
#12
Jinsung Hong, Sricharan Murugesan, Eric Betzig, John A Hammer
Mechano-transduction is an emerging but still poorly understood component of T cell activation. Here we investigated the ligand-dependent contribution made by contractile actomyosin arcs populating the peripheral supramolecular activation cluster (pSMAC) region of the immunological synapse (IS) to T cell receptor (TCR) microcluster transport and proximal signaling in primary mouse T cells. Using super resolution microscopy, OT1-CD8+ mouse T cells, and two ovalbumin (OVA) peptides with different affinities for the TCR, we show that the generation of organized actomyosin arcs depends on ligand potency and the ability of myosin 2 to contract actin filaments...
2017: PloS One
https://www.readbyqxmd.com/read/28790195/the-tyrosine-phosphatase-shp-1-promotes-t-cell-adhesion-by-activating-the-adaptor-protein-crkii-in-the-immunological-synapse
#13
Inbar Azoulay-Alfaguter, Marianne Strazza, Michael Peled, Hila K Novak, James Muller, Michael L Dustin, Adam Mor
The adaptor protein CrkII regulates T cell adhesion by recruiting the guanine nucleotide exchange factor C3G, an activator of Rap1. Subsequently, Rap1 stimulates the integrin LFA-1, which leads to T cell adhesion and interaction with antigen-presenting cells (APCs). The adhesion of T cells to APCs is critical for their proper function and education. The interface between the T cell and the APC is known as the immunological synapse. It is characterized by the specific organization of proteins that can be divided into central supramolecular activation clusters (c-SMACs) and peripheral SMACs (p-SMACs)...
August 8, 2017: Science Signaling
https://www.readbyqxmd.com/read/28771673/activity-of-lenalidomide-in-mantle-cell-lymphoma-can-be-explained-by-nk-cell-mediated-cytotoxicity
#14
Patrick R Hagner, Hsiling Chiu, Maria Ortiz, Benedetta Apollonio, Maria Wang, Suzana Couto, Michelle F Waldman, Erin Flynt, Alan G Ramsay, Matthew Trotter, Anita K Gandhi, Rajesh Chopra, Anjan Thakurta
Lenalidomide is an immunomodulatory agent that has demonstrated clinical benefit for patients with relapsed or refractory mantle cell lymphoma (MCL); however, despite this observed clinical activity, the mechanism of action (MOA) of lenalidomide has not been characterized in this setting. We investigated the MOA of lenalidomide in clinical samples from patients enrolled in the CC-5013-MCL-002 trial (NCT00875667) comparing single-agent lenalidomide versus investigator's choice single-agent therapy and validated our findings in pre-clinical models of MCL...
August 2, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28716933/cortical-actin-recovery-at-the-immunological-synapse-leads-to-termination-of-lytic-granule-secretion-in-cytotoxic-t-lymphocytes
#15
Alex T Ritter, Senta M Kapnick, Sricharan Murugesan, Pamela L Schwartzberg, Gillian M Griffiths, Jennifer Lippincott-Schwartz
CD8(+) cytotoxic T lymphocytes (CTLs) eliminate virally infected cells through directed secretion of specialized lytic granules. Because a single CTL can kill multiple targets, degranulation must be tightly regulated. However, how CTLs regulate the termination of granule secretion remains unclear. Previous work demonstrated that centralized actin reduction at the immune synapse precedes degranulation. Using a combination of live confocal, total internal reflection fluorescence, and superresolution microscopy, we now show that, after granule fusion, actin recovers at the synapse and no further secretion is observed...
August 8, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28713376/myristoylation-an-important-protein-modification-in-the-immune-response
#16
REVIEW
Daniel Ikenna Udenwobele, Ruey-Chyi Su, Sara V Good, Terry Blake Ball, Shailly Varma Shrivastav, Anuraag Shrivastav
Protein N-myristoylation is a cotranslational lipidic modification specific to the alpha-amino group of an N-terminal glycine residue of many eukaryotic and viral proteins. The ubiquitous eukaryotic enzyme, N-myristoyltransferase, catalyzes the myristoylation process. Precisely, attachment of a myristoyl group increases specific protein-protein interactions leading to subcellular localization of myristoylated proteins with its signaling partners. The birth of the field of myristoylation, a little over three decades ago, has led to the understanding of the significance of protein myristoylation in regulating cellular signaling pathways in several biological processes especially in carcinogenesis and more recently immune function...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28711300/raft-dependent-endocytic-movement-and-intracellular-cluster-formation-during-t%C3%A2-cell-activation-triggered-by-concanavalin-a
#17
Satomi Yabuuchi, Satoshi Endo, KeangOk Baek, Kunihide Hoshino, Yoshio Tsujino, Mun'delanji C Vestergaard, Masahiro Takagi
Certain food ingredients can stimulate the human immune system. A lectin, concanavalin A (ConA), from Canavalia ensiformis (jack bean) is one of the most well-known food-derived immunostimulants and mediates activation of cell-mediated immunity through T cell proliferation. Generally, T cell activation is known to be triggered by the interaction between T cells and antigen-presenting cells (APCs) via a juxtacrine (contact-dependent) signaling pathway. The mechanism has been well characterized and is referred to as formation of the immunological synapse (IS)...
July 12, 2017: Journal of Bioscience and Bioengineering
https://www.readbyqxmd.com/read/28696300/acetylcholine-producing-nk-cells-attenuate-cns-inflammation-via-modulation-of-infiltrating-monocytes-macrophages
#18
Wei Jiang, Daojing Li, Ranran Han, Chao Zhang, Wei-Na Jin, Kristofer Wood, Qiang Liu, Fu-Dong Shi, Junwei Hao
The nonneural cholinergic system of immune cells is pivotal for the maintenance of immunological homeostasis. Here we demonstrate the expression of choline acetyltransferase (ChAT) and cholinergic enzymes in murine natural killer (NK) cells. The capacity for acetylcholine synthesis by NK cells increased markedly under inflammatory conditions such as experimental autoimmune encephalomyelitis (EAE), in which ChAT expression escalated along with the maturation of NK cells. ChAT(+) and ChAT(-) NK cells displayed distinctive features in terms of cytotoxicity and chemokine/cytokine production...
July 25, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28692472/quantification-of-immune-dysregulation-by-next-generation-polymerase-chain-reaction-to-improve-sepsis-diagnosis-in-surgical-patients
#19
Raquel Almansa, Alicia Ortega, Ana Ávila-Alonso, Maria Heredia-Rodríguez, Silvia Martín, Diana Benavides, Marta Martín-Fernandez, Lucia Rico, César Aldecoa, Jesús Rico, Iñigo López de Cenarruzabeitia, Juan Beltrán de Heredia, Esther Gomez-Sanchez, Marta Aragón, Cristina Andrés, Dolores Calvo, David Andaluz-Ojeda, Pilar Liu, Francisco Blanco-Antona, Lydia Blanco, Jose Ignacio Gómez-Herreras, Eduardo Tamayo, Jesus F Bermejo-Martin
OBJECTIVES: To quantify immunological dysfunction in surgical patients with presence/absence of sepsis using a droplet digital polymerase chain reaction (ddPCR) transcriptomic analysis. The study also aims to evaluate this approach for improving identification of sepsis in these patients. BACKGROUND: Immune dysregulation is a central event in sepsis. Quantification of the expression of immunological genes participating in the pathogenesis of sepsis could represent a new avenue to improve its diagnosis...
July 7, 2017: Annals of Surgery
https://www.readbyqxmd.com/read/28691087/cytoskeletal-actin-dynamics-shape-a-ramifying-actin-network-underpinning-immunological-synapse-formation
#20
Marco Fritzsche, Ricardo A Fernandes, Veronica T Chang, Huw Colin-York, Mathias P Clausen, James H Felce, Silvia Galiani, Christoph Erlenkämper, Ana M Santos, John M Heddleston, Isabela Pedroza-Pacheco, Dominic Waithe, Jorge Bernardino de la Serna, B Christoffer Lagerholm, Tsung-Li Liu, Teng-Leong Chew, Eric Betzig, Simon J Davis, Christian Eggeling
T cell activation and especially trafficking of T cell receptor microclusters during immunological synapse formation are widely thought to rely on cytoskeletal remodeling. However, important details on the involvement of actin in the latter transport processes are missing. Using a suite of advanced optical microscopes to analyze resting and activated T cells, we show that, following contact formation with activating surfaces, these cells sequentially rearrange their cortical actin across the entire cell, creating a previously unreported ramifying actin network above the immunological synapse...
June 2017: Science Advances
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