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https://www.readbyqxmd.com/read/28918491/dynamics-of-allosteric-modulation-of%C3%A2-lymphocyte-function-associated-antigen-1-closure-open-switch-unveiling-the-structural-mechanisms-associated-with-outside-in-signaling-activation
#1
Maryam Abdullahi, Fisayo A Olotu, Mahmoud E Soliman
OBJECTIVES: To provide insight into the dynamics of the shape-shifting mechanistic events associated with the opening (activation) of Lymphocyte Function Associated Antigen-1 upon allosteric modulation by an activator, ICAM Binding Enhancer-667 (IBE-667), using molecular dynamics simulation. RESULTS: Various parameters were used to appropriately describe and understand the sequence of events that characterized its activation across the simulation period such as residual distances, TriCα angles; as well as the dihedral angle...
September 16, 2017: Biotechnology Letters
https://www.readbyqxmd.com/read/28910956/-modulation-of-umbilical-cord-blood-mesenchymal-stem-cells-on-treg-cells-in-the-patients-with-aplastic-anemia
#2
Y N Cao, F Zhou, N X Song, Y Fang, R Guan
Objective: To research the modulation of Umbilical cord blood mesenchymal stem cells on the number and function of Treg cells in the patients with aplastic anemia, as well as the expression of LFA-1 on Treg cells. Methods: A total of 20 newly diagnosed NSAA patients were collected from May 2015 to Jun 2016 in Department of Hematopathy, General Hospital of Jinan Military, and 10 healthy volunteers were recruited as controls. Separation of the patients and controls with peripheral blood mononuclear cells were divided into two groups, including PBMCs culture alone, PBMCs co-culture with UC-MSCs, application of flow cytometry detect respectively the proportion of the Treg cells and the expression of LFA-1 on Treg cells under different culture conditions...
September 12, 2017: Zhonghua Yi Xue za Zhi [Chinese medical journal]
https://www.readbyqxmd.com/read/28881670/g-csf-inhibits-lfa-1-mediated-cd4-t-cell-functions-by-inhibiting-lck-and-zap-70
#3
Shasha Zhao, Zhenyang Gu, Li Wang, Lixun Guan, Feiyan Wang, Nan Yang, Lan Luo, Zhe Gao, Yingwei Song, Lili Wang, Daihong Liu, Chunji Gao
In this study, we showed that G-CSF mobilization increased the frequency of T cells, specifically CD3(+)CD4(+) T cells. G-CSF mobilization decreased the secretion of inflammatory cytokines of CD4(+) T cells through the LFA-1/ICAM-1 signaling pathway, whereas it did not alter the TH1/TH2 ratio. We found that G-CSF mobilization inhibited LFA-1-mediated CD4(+) T cell polarization and motility. In vitro, G-CSF stimulation also attenuated the polarization and adhesiveness of CD4(+) T cells through the LFA-1/ICAM-1 interaction...
August 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/28875936/high-mtor-activity-is-a-hallmark-of-reactive-natural-killer-cells-and-amplifies-early-signaling-through-activating-receptors
#4
Antoine Marçais, Marie Marotel, Sophie Degouve, Alice Koenig, Sébastien Fauteux-Daniel, Annabelle Drouillard, Heinrich Schlums, Sébastien Viel, Laurie Besson, Omran Allatif, Mathieu Bléry, Eric Vivier, Yenan Bryceson, Olivier Thaunat, Thierry Walzer
NK cell education is the process through which chronic engagement of inhibitory NK cell receptors by self MHC-I molecules preserves cellular responsiveness. The molecular mechanisms responsible for NK cell education remain unclear. Here, we show that mouse NK cell education is associated with a higher basal activity of the mTOR/Akt pathway, commensurate to the number of educating receptors. This higher activity was dependent on the SHP-1 phosphatase and essential for the improved responsiveness of reactive NK cells...
August 30, 2017: ELife
https://www.readbyqxmd.com/read/28872666/active-dissemination-of-cellular-antigens-by-dcs-facilitates-cd8-t-cell-priming-in-lymph-nodes
#5
Irina Gurevich, Tali Feferman, Idan Milo, Orna Tal, Ofra Golani, Ingo Drexler, Guy Shakhar
Antigen (Ag)-specific activation of naïve T cells by migrating dendritic cells (DCs) is a highly efficient process, although the chances for their co-localization in lymph nodes (LNs) appear low. Ag presentation may be delegated from Ag-donor DCs to the abundant resident DCs, but the routes of Ag transfer and how it facilitates T-cell activation remain unclear. We visualized CD8(+) T cell-DC interactions to study the sites, routes and cells mediating Ag transfer in mice. In vitro, Ag transfer from isolated ovalbumin (OVA)(+) bone marrow (BM)-DCs triggered widespread arrest, Ca(2+) flux and CD69 upregulation in OT-I T cells contacting recipient DCs...
September 5, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28871263/the-activity-of-the-neutral-sphingomyelinase-is-important-in-t-cell-recruitment-and-directional-migration
#6
Lena Collenburg, Niklas Beyersdorf, Teresa Wiese, Christoph Arenz, Essa M Saied, Katrin Anne Becker-Flegler, Sibylle Schneider-Schaulies, Elita Avota
Breakdown of sphingomyelin as catalyzed by the activity of sphingomyelinases profoundly affects biophysical properties of cellular membranes which is particularly important with regard to compartmentalization of surface receptors and their signaling relay. As it is activated both upon TCR ligation and co-stimulation in a spatiotemporally controlled manner, the neutral sphingomyelinase (NSM) has proven to be important in T cell activation, where it appears to play a particularly important role in cytoskeletal reorganization and cell polarization...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28851628/pde8-controls-cd4-t-cell-motility-through-the-pde8a-raf-1-kinase-signaling-complex
#7
Chaitali P Basole, Rebecca K Nguyen, Katie Lamothe, Amanda Vang, Robert Clark, George S Baillie, Paul M Epstein, Stefan Brocke
The levels of cAMP are regulated by phosphodiesterase enzymes (PDEs), which are targets for the treatment of inflammatory disorders. We have previously shown that PDE8 regulates T cell motility. Here, for the first time, we report that PDE8A exerts part of its control of T cell function through the V-raf-1 murine leukemia viral oncogene homolog 1 (Raf-1) kinase signaling pathway. To examine T cell motility under physiologic conditions, we analyzed T cell interactions with endothelial cells and ligands in flow assays...
August 26, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28845904/spreading-the-load-antigen-transfer-between-migratory-and-lymph-node-resident-dendritic-cells-promotes-t-cell-priming
#8
Scott N Mueller
Dendritic cells (DC) are specialized in the processing and presentation of antigen for the activation of lymphocytes. Multiple subsets of DCs exist with distinct functions and roles in the initiation of immune responses. DCs found within tissues acquire antigens or become infected by pathogens and migrate to local draining lymph nodes (LN) where they can directly stimulate T cells. These migratory DCs can also transfer antigens to LN-resident DCs and may indirectly enhance T cell priming. In this issue of the European Journal of Immunology, Gurevich et al...
August 28, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28831022/the-adaptor-molecule-riam-integrates-signaling-events-critical-for-integrin-mediated-control-of-immune-function-and-cancer-progression
#9
REVIEW
Nikolaos Patsoukis, Kankana Bardhan, Jessica D Weaver, Duygu Sari, Alvaro Torres-Gomez, Lequn Li, Laura Strauss, Esther M Lafuente, Vassiliki A Boussiotis
Lymphocyte activation requires adhesion to antigen-presenting cells. This is a critical event linking innate and adaptive immunity. Lymphocyte adhesion is accomplished through LFA-1, which must be activated by a process referred to as inside-out integrin signaling. Among the few signaling molecules that have been implicated in inside-out integrin activation in hematopoietic cells are the small guanosine triphosphatase (GTPase) Rap1 and its downstream effector Rap1-interacting molecule (RIAM), a multidomain protein that defined the Mig10-RIAM-lamellipodin (MRL) class of adaptor molecules...
August 22, 2017: Science Signaling
https://www.readbyqxmd.com/read/28798145/tnf-induces-neutrophil-adhesion-via-formin-dependent-cytoskeletal-reorganization-and-activation-of-%C3%AE-integrin-function
#10
Angélica Aparecida Antoniellis Silveira, Venina Marcela Dominical, Camila Bononi Almeida, Hanan Chweih, Wilson Alves Ferreira, Cristina Pontes Vicente, Fabio Trindade Maranhão Costa, Claudio C Werneck, Fernando Ferreira Costa, Nicola Conran
Although essential for inflammatory responses, leukocyte recruitment to blood vessel walls in response to inflammatory stimuli, such as TNF-α, can contribute to vascular occlusion in inflammatory diseases, including atherosclerosis. We aimed to further characterize the mechanisms by which TNF stimulates adhesive and morphologic alterations in neutrophils. Microfluidic and intravital assays confirmed the potent effect that TNF has on human and murine neutrophil adhesion and recruitment in vitro and in vivo, respectively...
August 10, 2017: Journal of Leukocyte Biology
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
#11
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/28765218/dengue-virus-infected-dendritic-cells-but-not-monocytes-activate-natural-killer-cells-through-a-contact-dependent-mechanism-involving-adhesion-molecules
#12
Vivian Vasconcelos Costa, Weijian Ye, Qingfeng Chen, Mauro Martins Teixeira, Peter Preiser, Eng Eong Ooi, Jianzhu Chen
Natural killer (NK) cells play a protective role against dengue virus (DENV) infection, but the cellular and molecular mechanisms are not fully understood. Using an optimized humanized mouse model, we show that human NK cells, through the secretion of gamma interferon (IFN-γ), are critical in the early defense against DENV infection. Depletion of NK cells or neutralization of IFN-γ leads to increased viremia and more severe thrombocytopenia and liver damage in humanized mice. In vitro studies using autologous human NK cells show that DENV-infected monocyte-derived dendritic cells (MDDCs), but not monocytes, activate NK cells in a contact-dependent manner, resulting in upregulation of CD69 and CD25 and secretion of IFN-γ...
August 1, 2017: MBio
https://www.readbyqxmd.com/read/28715655/macrophage-exosomes-as-natural-nanocarriers-for-protein-delivery-to-inflamed-brain
#13
Dongfen Yuan, Yuling Zhao, William A Banks, Kristin M Bullock, Matthew Haney, Elena Batrakova, Alexander V Kabanov
Recent work has stimulated interest in the use of exosomes as nanocarriers for delivery of small drugs, RNAs, and proteins to the central nervous system (CNS). To overcome the blood-brain barrier (BBB), exosomes were modified with brain homing peptides that target brain endothelium but likely to increase immune response. Here for the first time we demonstrate that there is no need for such modification to penetrate the BBB in mammals. The naïve macrophage (Mϕ) exosomes can utilize, 1) on the one hand, the integrin lymphocyte function-associated antigen 1 (LFA-1) and intercellular adhesion molecule 1 (ICAM-1), and, 2) on the other hand, the carbohydrate-binding C-type lectin receptors, to interact with brain microvessel endothelial cells comprising the BBB...
October 2017: Biomaterials
https://www.readbyqxmd.com/read/28714582/altered-levels-of-soluble-cd18-may-associate-immune-mechanisms-with-outcome-in-sepsis
#14
T W Kragstrup, K Juul-Madsen, S H Christiansen, X Zhang, J Krog, T Vorup-Jensen, A G Kjaergaard
The pathogenesis of sepsis involves a dual inflammatory response, with a hyperinflammatory phase followed by, or in combination with, a hypoinflammatory phase. The adhesion molecules lymphocyte function-associated antigen (LFA-1) (CD11a/CD18) and macrophage-1 (Mac-1) (CD11b/CD18) support leucocyte adhesion to intercellular adhesion molecules and phagocytosis through complement opsonization, both processes relevant to the immune response during sepsis. Here, we investigate the role of soluble (s)CD18 in sepsis with emphasis on sCD18 as a mechanistic biomarker of immune reactions and outcome of sepsis...
July 17, 2017: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/28712928/bone-marrow-derived-mesenchymal-stem-cells-propagate-immunosuppressive-anti-inflammatory-macrophages-in-cell-to-cell-contact-independent-and-dependent-manners-under-hypoxic-culture
#15
Naoki Takizawa, Naoto Okubo, Masaharu Kamo, Naoyuki Chosa, Toshinari Mikami, Keita Suzuki, Seiji Yokota, Miho Ibi, Masato Ohtsuka, Masayuki Taira, Takashi Yaegashi, Akira Ishisaki, Seiko Kyakumoto
Immunosuppressive/anti-inflammatory macrophage (Mφ), M2-Mφ that expressed the typical M2-Mφs marker, CD206, and anti-inflammatory cytokine, interleukin (IL)-10, is beneficial and expected tool for the cytotherapy against inflammatory diseases. Here, we demonstrated that bone marrow-derived lineage-positive (Lin+) blood cells proliferated and differentiated into M2-Mφs by cooperation with the bone marrow-derived mesenchymal stem cells (MSCs) under hypoxic condition: MSCs not only promoted proliferation of undifferentiated M2-Mφs, pre-M2-Mφs, in the Lin+ fraction via a proliferative effect of the MSCs-secreted macrophage colony-stimulating factor, but also promoted M2-Mφ polarization of the pre-M2-Mφs through cell-to-cell contact with the pre-M2-Mφs...
July 14, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28707003/up-regulation-of-lfa-1-allows-liver-resident-memory-t-cells-to-patrol-and-remain-in-the-hepatic-sinusoids
#16
H A McNamara, Y Cai, M V Wagle, Y Sontani, C M Roots, L A Miosge, J H O'Connor, H J Sutton, V V Ganusov, W R Heath, P Bertolino, C G Goodnow, I A Parish, A Enders, I A Cockburn
Liver-resident CD8+ T cells are highly motile cells that patrol the vasculature and provide protection against liver pathogens. A key question is: how can these liver CD8+ T cells be simultaneously present in the circulation and tissue-resident? Because liver-resident T cells do not express CD103 - a key integrin for T cell residence in epithelial tissues - we investigated other candidate adhesion molecules. Using intra-vital imaging we found that CD8+ T cell patrolling in the hepatic sinusoids is dependent upon LFA-1-ICAM-1 interactions...
March 2017: Science Immunology
https://www.readbyqxmd.com/read/28706510/natural-killer-cell-functions-during-the-innate-immune-response-to-pathogenic-streptococci
#17
Paul Lemire, Tristan Galbas, Jacques Thibodeau, Mariela Segura
Dendritic cells (DCs) and NK cells play a crucial role in the first phase of host defense against infections. Group B Streptococcus (GBS) and Streptococcus suis are encapsulated streptococci causing severe systemic inflammation, leading to septicemia and meningitis. Yet, the involvement of NK cells in the innate immune response to encapsulated bacterial infection is poorly characterized. Here, it was observed that these two streptococcal species rapidly induce the release of IFN-γ and that NK cells are the major cell type responsible for this production during the acute phase of the infection...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28699640/lfa-1-activates-focal-adhesion-kinases-fak1-pyk2-to-generate-lat-grb2-skap1-complexes-that-terminate-t-cell-conjugate-formation
#18
Monika Raab, Yuning Lu, Karsten Kohler, Xin Smith, Klaus Strebhardt, Christopher E Rudd
Lymphocyte function-associated antigen 1 (LFA-1) affinity and avidity changes have been assumed to mediate adhesion to intercellular adhesion molecule-1 for T-cell conjugation to dendritic cells (DC). Although the T-cell receptor (TCR) and LFA-1 can generate intracellular signals, the immune cell adaptor protein linker for the activation of T cells (LAT) couples the TCR to downstream events. Here, we show that LFA-1 can mediate both adhesion and de-adhesion, dependent on receptor clustering. Although increased affinity mediates adhesion, LFA-1 cross-linking induced the association and activation of the protein-tyrosine kinases FAK1/PYK1 that phosphorylated LAT selectively on a single Y-171 site for the binding to adaptor complex GRB-2-SKAP1...
July 12, 2017: Nature Communications
https://www.readbyqxmd.com/read/28685587/3-dimensional-nano-fibre-scaffold-for-ex-vivo-expansion-of-cord-blood-haematopoietic-stem-cells
#19
Seyed Hadi Mousavi, Saeid Abroun, Masoud Soleimani, Seyed Javad Mowla
Cord blood (CB) haematopoietic stem cell (HSC) is an alternative source of HSC transplantation. The limited cell number greatly restricts their clinic-scale therapeutic applications. The objective of this study was an ex vivo expansion of CB HSCs in a new three-dimensional polycaprolactone nano-scaffold coated with fibronectin (FN). First, we isolated CB CD34+ cells and cultured 10 days in presence of growth factors. The evaluation was performed by qRT-PCR, flow cytometry and clonogenicity. 3D PCL nano-scaffold coated with FN produced significantly higher total nucleated cells and CD34+ cells (p < ...
July 7, 2017: Artificial Cells, Nanomedicine, and Biotechnology
https://www.readbyqxmd.com/read/28637901/caveolin-1-influences-lfa-1-redistribution-upon-tcr-stimulation-in-cd8-t-cells
#20
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...
August 1, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
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