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Immunological synapse

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https://www.readbyqxmd.com/read/28716933/cortical-actin-recovery-at-the-immunological-synapse-leads-to-termination-of-lytic-granule-secretion-in-cytotoxic-t-lymphocytes
#1
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...
July 17, 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
#2
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
#3
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
#4
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 10, 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
#5
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
#6
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
https://www.readbyqxmd.com/read/28690878/the-guanine-nucleotide-exchange-factor-caldag-gefi-fine-tunes-functional-properties-of-regulatory-t-cells
#7
Jana Niemz, Stefanie Kliche, Marina C Pils, Eliot Morrison, Annika Manns, Christian Freund, Jill R Crittenden, Ann M Graybiel, Melanie Galla, Lothar Jänsch, Jochen Huehn
Using quantitative phosphopeptide sequencing of unstimulated versus stimulated primary murine Foxp3(+) regulatory and Foxp3(-) conventional T cells (Tregs and Tconv, respectively), we detected a novel and differentially regulated tyrosine phosphorylation site within the C1 domain of the guanine-nucleotide exchange factor CalDAG GEFI. We hypothesized that the Treg-specific and activation-dependent reduced phosphorylation at Y523 allows binding of CalDAG GEFI to diacylglycerol, thereby impacting the formation of a Treg-specific immunological synapse...
June 2017: European Journal of Microbiology & Immunology
https://www.readbyqxmd.com/read/28688208/human-profilin-1-is-a-negative-regulator-of-ctl-mediated-cell-killing-and-migration
#8
Rouven Schoppmeyer, Renping Zhao, He Cheng, Mohamed Hamed, Chen Liu, Xiao Zhou, Eva C Schwarz, Yan Zhou, Arne Knörck, Gertrud Schwär, Shunrong Ji, Liang Liu, Jiang Long, Volkhard Helms, Markus Hoth, Xianjun Yu, Bin Qu
The actin-binding protein profilin1 (PFN1) plays a central role in actin dynamics, which is essential for cytotoxic T lymphocyte (CTL) functions. The functional role of PFN1 in CTLs, however still remains elusive. Here, we identify PFN1 as the only member of the profilin family expressed in primary human CD8(+) T cells. Using in vitro assays, we find that PFN1 is a negative regulator of CTL-mediated elimination of target cells. Furthermore, PFN1 is involved in activation-induced lytic granule (LG) release, CTL migration and modulation of actin structures at the immunological synapse (IS)...
July 8, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28665401/pd-l1-and-iaps-co-operate-to-protect-tumors-from-cytotoxic-lymphocyte-derived-tnf
#9
Conor J Kearney, Najoua Lalaoui, Andrew J Freeman, Kelly M Ramsbottom, John Silke, Jane Oliaro
Smac-mimetics are emerging as promising anti-cancer agents and are being evaluated in clinical trials for a variety of malignancies. Smac-mimetics can induce TNF production from a subset of tumor cells and simultaneously sensitize them to TNF-induced apoptosis. However, TNF derived from other cellular sources, such as cytotoxic lymphocytes (CLs) within the tumor, may also contribute to the anti-tumor activity of SMs. Here, we show that CD8(+) T cells and NK cells potently kill tumor cells in the presence of the SM, birinapant...
June 30, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28663103/quantitative-imaging-approaches-to-study-the-car-immunological-synapse
#10
REVIEW
Malini Mukherjee, Emily M Mace, Alexandre F Carisey, Nabil Ahmed, Jordan S Orange
The lytic immunological synapse (IS) is a discrete structural entity formed after the ligation of specific activating receptors that leads to the destruction of a cancerous cell. The formation of an effector cell IS in cytotoxic T lymphocytes or natural killer cells is a hierarchical and stepwise rearrangement of structural and signaling components and targeted release of the contents of lytic granules. While recent advances in the generation and testing of cytotoxic lymphocytes expressing chimeric antigen receptors (CARs) has demonstrated their efficacy in the targeted lysis of tumor targets, the contribution and dynamics of IS components have not yet been extensively investigated in the context of engineered CAR cells...
June 26, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28652577/human-in-vitro-induced-regulatory-t-cells-display-dlgh1dependent-and-pkc-%C3%AE-restrained-suppressive-activity
#11
Alexandra Zanin-Zhorov, Sudha Kumari, Keli L Hippen, Sarah C Merkel, Margaret L MacMillan, Bruce R Blazar, Michael L Dustin
In vitro induced human regulatory T cells (iTregs) have demonstrated in vivo therapeutic utility, but pathways regulating their function have not been elucidated. Here, we report that human iTregs generated in vitro from naïve cord blood cells preferentially recruit Disc large homolog 1 (Dlgh1) and exclude protein kinase C (PKC)-θ from immunological synapses formed on supported lipid bilayers with laterally mobile ICAM-1 and anti-CD3 mAb. Also, iTregs display elevated Dlgh1 overall and Dlgh1-dependent p38 phosphorylation, higher levels of phosphatase and tensin homolog (PTEN), and diminished Akt phosphorylation...
June 26, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28647138/think-like-a-sponge-the-genetic-signal-of-sensory-cells-in-sponges
#12
REVIEW
Jasmine L Mah, Sally P Leys
A complex genetic repertoire underlies the apparently simple body plan of sponges. Among the genes present in poriferans are those fundamental to the sensory and nervous systems of other animals. Sponges are dynamic and sensitive animals and it is intuitive to link these genes to behaviour. The proposal that ctenophores are the earliest diverging metazoan has led to the question of whether sponges possess a 'pre-nervous' system or have undergone nervous system loss. Both lines of thought generally assume that the last common ancestor of sponges and eumetazoans possessed the genetic modules that underlie sensory abilities...
June 21, 2017: Developmental Biology
https://www.readbyqxmd.com/read/28646361/erratum-to-chimeric-antigen-receptor-car-modified-natural-killer-cell-based-immunotherapy-and-immunological-synapse-formation-in-cancer-and-hiv
#13
Dongfang Liu, Shuo Tian, Kai Zhang, Wei Xiong, Ndongala Michel Lubaki, Zhiying Chen, Weidong Han
No abstract text is available yet for this article.
June 23, 2017: Protein & Cell
https://www.readbyqxmd.com/read/28642595/3d-bayesian-cluster-analysis-of-super-resolution-data-reveals-lat-recruitment-to-the-t-cell-synapse
#14
Juliette Griffié, Leigh Shlomovich, David J Williamson, Michael Shannon, Jesse Aaron, Satya Khuon, Garth L Burn, Lies Boelen, Ruby Peters, Andrew P Cope, Edward A K Cohen, Patrick Rubin-Delanchy, Dylan M Owen
Single-molecule localisation microscopy (SMLM) allows the localisation of fluorophores with a precision of 10-30 nm, revealing the cell's nanoscale architecture at the molecular level. Recently, SMLM has been extended to 3D, providing a unique insight into cellular machinery. Although cluster analysis techniques have been developed for 2D SMLM data sets, few have been applied to 3D. This lack of quantification tools can be explained by the relative novelty of imaging techniques such as interferometric photo-activated localisation microscopy (iPALM)...
June 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28637901/caveolin-1-influences-lfa-1-redistribution-upon-tcr-stimulation-in-cd8-t-cells
#15
Jessica G Borger, Vicky L Morrison, Andrew Filby, Celine Garcia, Liisa M Uotila, Fabio Simbari, Susanna C Fagerholm, Rose Zamoyska
TCR stimulation by peptide-MHC complexes on APCs requires precise reorganization of molecules into the area of cellular contact to form an immunological synapse from where T cell signaling is initiated. Caveolin (Cav)1, a widely expressed transmembrane protein, is involved in the regulation of membrane composition, cellular polarity and trafficking, and the organization of signal transduction pathways. The presence of Cav1 protein in T cells was identified only recently, and its function in this context is not well understood...
June 21, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28637489/synaptoimmunology-roles-in-health-and-disease
#16
REVIEW
Robert Nisticò, Eric Salter, Celine Nicolas, Marco Feligioni, Dalila Mango, Zuner A Bortolotto, Pierre Gressens, Graham L Collingridge, Stephane Peineau
Mounting evidence suggests that the nervous and immune systems are intricately linked. Many proteins first identified in the immune system have since been detected at synapses, playing different roles in normal and pathological situations. In addition, novel immunological functions are emerging for proteins typically expressed at synapses. Under normal conditions, release of inflammatory mediators generally represents an adaptive and regulated response of the brain to immune signals. On the other hand, when immune challenge becomes prolonged and/or uncontrolled, the consequent inflammatory response leads to maladaptive synaptic plasticity and brain disorders...
June 20, 2017: Molecular Brain
https://www.readbyqxmd.com/read/28624961/phenotypic-and-functional-characterization-of-t-cells-in-white-matter-lesions-of-multiple-sclerosis-patients
#17
Gijsbert P van Nierop, Marvin M van Luijn, Samira S Michels, Marie-Jose Melief, Malou Janssen, Anton W Langerak, Werner J D Ouwendijk, Rogier Q Hintzen, Georges M G M Verjans
T cells are considered pivotal in the pathology of multiple sclerosis (MS), but their function and antigen specificity are unknown. To unravel the role of T cells in MS pathology, we performed a comprehensive analysis on T cells recovered from paired blood, cerebrospinal fluid (CSF), normal-appearing white matter (NAWM) and white matter lesions (WML) from 27 MS patients with advanced disease shortly after death. The differentiation status of T cells in these compartments was determined by ex vivo flow cytometry and immunohistochemistry...
June 17, 2017: Acta Neuropathologica
https://www.readbyqxmd.com/read/28608562/t11ts-immunotherapy-repairs-pi3k-akt-signaling-in-t-cells-clues-towards-enhanced-t-cell-survival-in-rat-glioma-model
#18
Suhnrita Chaudhuri, Manoj Kumar Singh, Debanjan Bhattacharya, Ankur Datta, Iman Hazra, Somnath Mondal, Omar Faruk Sk Md, Larance Ronsard, Tushar Kanti Ghosh, Swapna Chaudhuri
Malignant glioma is the most fatal of astrocytic lineage tumors despite therapeutic advances. Onset and progression of gliomas is accompanied by severe debilitation of T-cell defense and T-cell survival. One of the chief contributors to T-cell survival downstream of activation is the PI3K-AKT pathway. Our prior studies showed that the novel immunotherapeutic molecule T11-target structure (T11TS) blocks T-cell apoptosis in glioma. We also showed activation of immunological synapse components and calcineurin-NFAT pathway following T11TS immunotherapy of glioma-bearing rats...
June 13, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28494186/small-interference-itga6-gene-targeting-in-the-human-thymic-epithelium-differentially-regulates-the-expression-of-immunological-synapse-related-genes
#19
Daiane Cristina F Golbert, Eliane Santana-Van-Vliet, Marcelo Ribeiro-Alves, Marbella Maria B da Fonsêca, Ailin Lepletier, Daniella Arêas Mendes-da-Cruz, Guilherme Loss, Vinícius Cotta-de-Almeida, Ana Tereza R Vasconcelos, Wilson Savino
The thymus supports differentiation of T cell precursors. This process requires relocation of developing thymocytes throughout multiple microenvironments of the organ, mainly with thymic epithelial cells (TEC), which control intrathymic T cell differentiation influencing the formation and maintenance of the immunological synapse. In addition to the proteins of the major histocompatibility complex (MHC), this structure is supported by several adhesion molecules. During the process of thymopoiesis, we previously showed that laminin-mediated interactions are involved in the entrance of T-cell precursors into the thymus, as well as migration of differentiating thymocytes within the organ...
May 11, 2017: Cell Adhesion & Migration
https://www.readbyqxmd.com/read/28488245/chimeric-antigen-receptor-car-modified-natural-killer-cell-based-immunotherapy-and-immunological-synapse-formation-in-cancer-and-hiv
#20
REVIEW
Dongfang Liu, Shuo Tian, Kai Zhang, Wei Xiong, Ndongala Michel Lubaki, Zhiying Chen, Weidong Han
Cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells contribute to the body's immune defenses. Current chimeric antigen receptor (CAR)-modified T cell immunotherapy shows strong promise for treating various cancers and infectious diseases. Although CAR-modified NK cell immunotherapy is rapidly gaining attention, its clinical applications are mainly focused on preclinical investigations using the NK92 cell line. Despite recent advances in CAR-modified T cell immunotherapy, cost and severe toxicity have hindered its widespread use...
May 9, 2017: Protein & Cell
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