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Immunological synapse

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https://www.readbyqxmd.com/read/29130972/human-dendritic-cells-with-th2-polarizing-capacity-analysis-using-label-free-quantitative-proteomics
#1
Leonie Hussaarts, Maria Mardalena Martini Kaisar, Arzu Tugce Guler, Hans Dalebout, Bart Everts, André M Deelder, Magnus Palmblad, Maria Yazdanbakhsh
BACKGROUND: Dendritic cells (DCs) are the sentinels of the immune system. Upon recognition of a pathogen, they mature and migrate to draining lymph nodes to prime and polarize T cell responses. Although it is known that helminths and helminth-derived molecules condition DCs to polarize T helper (Th) cells towards Th2, the underlying mechanisms remain incompletely understood. OBJECTIVES: The aim of this study was to conduct a proteome analysis of helminth antigen-stimulated DCs in order to gain more insight into the cellular processes associated with their ability to polarize immune responses...
November 10, 2017: International Archives of Allergy and Immunology
https://www.readbyqxmd.com/read/29123958/expression-of-cd94-by-ex-vivo-differentiated-nk-cells-correlates-with-the-in-vitro-and-in-vivo-acquisition-of-cytotoxic-features
#2
Meriem Hasmim, Nadine Khalife, Yanyan Zhang, Manale Doldur, Geralidne Visentin, Stéphane Terry, Julien Giron-Michel, Ruoping Tang, François Delhommeau, Nicolas Dulphy, Jean-Henri Bourhis, Fawzia Louache, Salem Chouaib
The administration of ex vivo-expanded Natural Killer (NK) cells in leukemia therapy is still challenging, in part due to the difficulty to generate in sufficient quantities fully mature and functional NK cells and Identification of surface markers indicative of NK maturation and functionality is therefore needed. Here, based on the analysis of surface receptors of ex vivo-expanded NK cells, we identified CD94 as a surface marker correlating with high lytic potential against leukemic cell lines and immunological synapse formation...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/29123650/transcellular-communication-at-the-immunological-synapse-a-vesicular-traffic-mediated-mutual-exchange
#3
REVIEW
Francesca Finetti, Chiara Cassioli, Cosima T Baldari
The cell's ability to communicate with the extracellular environment, with other cells, and with itself is a crucial feature of eukaryotic organisms. In the immune system, T lymphocytes assemble a specialized structure upon contact with antigen-presenting cells bearing a peptide-major histocompatibility complex ligand, known as the immunological synapse (IS). The IS has been extensively characterized as a signaling platform essential for T-cell activation. Moreover, emerging evidence identifies the IS as a device for vesicular traffic-mediated cell-to-cell communication as well as an active release site of soluble molecules...
2017: F1000Research
https://www.readbyqxmd.com/read/29120926/recent-insights-into-biological-functions-of-mammalian-bombesin-like-peptides-and-their-receptors
#4
Xiangping Qu, Hui Wang, Rujiao Liu
PURPOSE OF REVIEW: The current review highlights recent advances in physiological and pharmacological researches in biology of mammalian bombesin-like peptides (BLPs). RECENT FINDINGS: BLPs and their receptors were found to have regulatory roles in many biological processes in central nervous system. Two BLPs, neuromedin B and gastrin-releasing peptide (GRP), and their receptors are required for regulation of basal and induced sighing activity in rodents. This is the first study demonstrating central pathways involved in regulation of sighing activity...
November 7, 2017: Current Opinion in Endocrinology, Diabetes, and Obesity
https://www.readbyqxmd.com/read/29079742/dual-biomembrane-force-probe-enables-single-cell-mechanical-analysis-of-signal-crosstalk-between-multiple-molecular-species
#5
Lining Ju, Yunfeng Chen, Kaitao Li, Zhou Yuan, Baoyu Liu, Shaun P Jackson, Cheng Zhu
Conventional approaches for studying receptor-mediated cell signaling, such as the western blot and flow cytometry, are limited in three aspects: 1) The perturbing preparation procedures often alter the molecules from their native state on the cell; 2) Long processing time before the final readout makes it difficult to capture transient signaling events (<1 min); 3) The experimental environments are force-free, therefore unable to visualize mechanical signals in real time. In contrast to these methods in biochemistry and cell biology that are usually population-averaged and non-real-time, here we introduce a novel single-cell based nanotool termed dual biomembrane force probe (dBFP)...
October 27, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29079655/reversible-transgene-expression-reduces-fratricide-and-permits-4-1bb-costimulation-of-car-t-cells-directed-to-t-cell-malignancies
#6
Maksim Mamonkin, Malini Mukherjee, Madhuwanti Srinivasan, Sandhya Sharma, Diogo Gomes-Silva, Feiyan Mo, Giedre Krenciute, Jordan S Orange, Malcolm K Brenner
T cells expressing second-generation chimeric antigen receptors (CARs) specific for CD5, a T-cell surface marker present on normal and malignant T cells, can selectively kill tumor cells. We aimed to improve this killing by substituting the CD28 costimulatory endodomain (28.z) with 4-1BB (BB.z), as 28.z CD5 CAR T cells rapidly differentiated into short-lived effector cells. In contrast, 4-1BB costimulation is known to promote development of the central memory subpopulation. Here, we found BB.z CD5 CAR T cells had impaired growth compared to 28...
October 27, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/29042364/a-cd200r-cd28-fusion-protein-appropriates-an-inhibitory-signal-to-enhance-t-cell-function-and-therapy-of-murine-leukemia
#7
Shannon K Oda, Andrew W Daman, Nicolas M Garcia, Felecia Wagener, Thomas M Schmitt, Xiaoxia Tan, Aude G Chapuis, Philip D Greenberg
Acute myeloid leukemia (AML), the most common adult acute leukemia in the U.S., has the poorest survival rate, with 26% of patients surviving 5 years. Adoptive immunotherapy with T cells genetically modified to recognize tumors is a promising and evolving treatment option. However, antitumor activity, particularly in the context of progressive leukemia, can be dampened both by limited costimulation and triggering of immunoregulatory checkpoints that attenuate T cell responses. Expression of CD200 (OX2), a negative regulator of T cell function that binds CD200R, is commonly increased in leukemia and other malignancies, and is associated with poor prognosis in leukemia patients...
October 17, 2017: Blood
https://www.readbyqxmd.com/read/29027226/efferocytosis-of-dying-cells-differentially-modulate-immunological-outcomes-in-tumor-microenvironment
#8
REVIEW
Sushil Kumar, David Calianese, Raymond B Birge
Programmed cell death (apoptosis) is an integral part of tissue homeostasis in complex organisms, allowing for tissue turnover, repair, and renewal while simultaneously inhibiting the release of self antigens and danger signals from apoptotic cell-derived constituents that can result in immune activation, inflammation, and autoimmunity. Unlike cells in culture, the physiological fate of cells that die by apoptosis in vivo is their rapid recognition and engulfment by phagocytic cells (a process called efferocytosis)...
November 2017: Immunological Reviews
https://www.readbyqxmd.com/read/29023539/despite-disorganized-synapse-structure-th2-cells-maintain-directional-delivery-of-cd40l-to-antigen-presenting-b-cells
#9
Jennifer L Gardell, David C Parker
Upon recognition of peptide displayed on MHC molecules, Th1 and Th2 cells form distinct immunological synapse structures. Th1 cells have a bull's eye synapse structure with TCR/ MHC-peptide interactions occurring central to a ring of adhesion molecules, while Th2 cells have a multifocal synapse with small clusters of TCR/MHC interactions throughout the area of T cell/antigen-presenting cell interaction. In this study, we investigated whether this structural difference in the immunological synapse affects delivery of T cell help...
2017: PloS One
https://www.readbyqxmd.com/read/28981993/membrane-lipid-order-of-sub-synaptic-t-cell-vesicles-correlates-with-their-dynamics-and-function
#10
George W Ashdown, David J Williamson, Gary H M Soh, Nathan Day, Garth L Burn, Dylan M Owen
During an immune response, T cells survey antigen presenting cells for antigenic peptides via the formation of an interface known as an immunological synapse. Among the complex and dynamic biophysical phenomena occurring at this interface is the trafficking of sub-synaptic vesicles carrying a variety of proximal signalling molecules. Here, we show that rather than being a homogeneous population, these vesicles display a diversity of membrane lipid order profiles, as measured using the environmentally sensitive dye di-4-ANEPPDHQ and multi-spectral TIRF microscopy...
October 5, 2017: Traffic
https://www.readbyqxmd.com/read/28978806/dock8-enforces-immunological-tolerance-by-promoting-il-2-signaling-and-immune-synapse-formation-in-tregs
#11
Erin Janssen, Sudha Kumari, Mira Tohme, Sumana Ullas, Victor Barrera, Jeroen Mj Tas, Marcela Castillo-Rama, Roderick T Bronson, Shariq M Usmani, Darrell J Irvine, Thorsten R Mempel, Raif S Geha
Patients deficient in the guanine nucleotide exchange factor DOCK8 have decreased numbers and impaired in vitro function of Tregs and make autoantibodies, but they seldom develop autoimmunity. We show that, similarly, Dock8-/- mice have decreased numbers and impaired in vitro function of Tregs but do not develop autoimmunity. In contrast, mice with selective DOCK8 deficiency in Tregs develop lymphoproliferation, autoantibodies, and gastrointestinal inflammation, despite a normal percentage and in vitro function of Tregs, suggesting that deficient T effector cell function might protect DOCK8-deficient patients from autoimmunity...
October 5, 2017: JCI Insight
https://www.readbyqxmd.com/read/28928741/cxcl12-mediates-aberrant-costimulation-of-b-lymphocytes-in-warts-hypogammaglobulinemia-infections-myelokathexis-immunodeficiency
#12
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
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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...
October 1, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
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