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https://www.readbyqxmd.com/read/29127148/ubc9-binds-to-adap-and-is-required-for-rap1-membrane-recruitment-rac1-activation-and-integrin-mediated-t-cell-adhesion
#1
Yiwei Xiong, Chengjin Ye, Naiqi Yang, Madanqi Li, Hebin Liu
Although the immune adaptor adhesion and degranulation-promoting adaptor protein (ADAP) acts as a key mediator of integrin inside-out signaling leading to T cell adhesion, the regulation of this adaptor during integrin activation and clustering remains unclear. We now identify Ubc9, the sole small ubiquitin-related modifier E2 conjugase, as an essential regulator of ADAP where it is required for TCR-induced membrane recruitment of the small GTPase Rap1 and its effector protein RapL and for activation of the small GTPase Rac1 in T cell adhesion...
November 10, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
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/29100055/extracellular-isg15-signals-cytokine-secretion-through-the-lfa-1-integrin-receptor
#3
Caleb D Swaim, Ariella F Scott, Larissa A Canadeo, Jon M Huibregtse
ISG15 is a ubiquitin-like protein that functions in innate immunity both as an intracellular protein modifier and as an extracellular signaling molecule that stimulates IFN-γ secretion. The extracellular function, important for resistance to mycobacterial disease, has remained biochemically uncharacterized. We have established an NK-92 cell-based assay for IFN-γ release, identified residues critical for ISG15 signaling, and identified the cell surface receptor as LFA-1 (CD11a/CD18; αLβ2 integrin). LFA-1 inhibition blocked IFN-γ secretion, splenocytes from CD11a(-/-) mice did not respond to ISG15, and ISG15 bound directly to the αI domain of CD11a in vitro...
November 2, 2017: Molecular Cell
https://www.readbyqxmd.com/read/29099772/role-of-lfa-1-and-icam-1-in-cancer
#4
REVIEW
Manuel Reina, Enric Espel
The lymphocyte function-associated antigen-1 (LFA-1) (also known as CD11a/CD18 and αLβ₂), is just one of many integrins in the human body, but its significance is derived from its exclusive presence in leukocytes. In this review, we summarize the studies relating LFA-1 and its major ligand ICAM-1 (or CD54) with cancer, through the function of lymphocytes and myeloid cells on tumor cells. We consider how LFA-1 mediates the interaction of leukocytes with tumors and the role of ICAM-1 in tumor dynamics, which can be independent of its interaction with LFA-1...
November 3, 2017: Cancers
https://www.readbyqxmd.com/read/29098911/targeted-treatments-for-hidradenitis-suppurativa-a-review-of-the-current-literature-and-ongoing-clinical-trials
#5
Melody Maarouf, Ashley K Clark, Dylan E Lee, Vivian Y Shi
PURPOSE: Targeted, immune-modulating drugs are at the forefront of therapy for HS, and a comprehensive clinical trial registry is needed to facilitate data pooling and clinical efficacy comparison. MATERIALS AND METHODS: A systematic review of the ClinicalTrials.gov database was searched for planned, in-progress, completed, or terminated trials investigating the effect of targeted biologic therapies for hidradenitis suppurativa (HS). When results of RCTs were not available, case reports or series were included...
November 10, 2017: Journal of Dermatological Treatment
https://www.readbyqxmd.com/read/29081775/lfa-1-mediates-cytotoxicity-and-tissue-migration-of-specific-cd8-t-cells-after-heterologous-prime-boost-vaccination-against-trypanosoma-cruzi-infection
#6
Camila Pontes Ferreira, Leonardo Moro Cariste, Fernando Dos Santos Virgílio, Barbara Ferri Moraschi, Caroline Brandão Monteiro, Alexandre M Vieira Machado, Ricardo Tostes Gazzinelli, Oscar Bruna-Romero, Pedro Luiz Menin Ruiz, Daniel Araki Ribeiro, Joseli Lannes-Vieira, Marcela de Freitas Lopes, Mauricio Martins Rodrigues, José Ronnie Carvalho de Vasconcelos
Integrins mediate the lymphocyte migration into an infected tissue, and these cells are essential for controlling the multiplication of many intracellular parasites such as Trypanosoma cruzi, the causative agent of Chagas disease. Here, we explore LFA-1 and VLA-4 roles in the migration of specific CD8(+) T cells generated by heterologous prime-boost immunization during experimental infection with T. cruzi. To this end, vaccinated mice were treated with monoclonal anti-LFA-1 and/or anti-VLA-4 to block these molecules...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29075657/impaired-t-cell-migration-to-the-cns-under-fingolimod-and-dimethyl-fumarate
#7
Amandine Mathias, Sylvain Perriot, Mathieu Canales, Claudia Blatti, Coline Gaubicher, Myriam Schluep, Britta Engelhardt, Renaud Du Pasquier
OBJECTIVE: To evaluate the long-term effects of treatments used in MS on the T-cell trafficking profile. METHODS: We enrolled 83 patients with MS under fingolimod (FTY), natalizumab (NTZ), dimethyl fumarate (DMF), or other disease-modifying treatments (DMTs). Blood was drawn before treatment onset and up to 36-48 months. The ex vivo expression of CNS-related integrins (α4β1 and αL subunit of LFA-1) and the gut-related integrin (α4β7) was assessed using flow cytometry on CD4(+) and CD8(+) T cells...
November 2017: Neurology® Neuroimmunology & Neuroinflammation
https://www.readbyqxmd.com/read/28972539/cd56bright-nk-cells-exhibit-potent-antitumor-responses-following-il-15-priming
#8
Julia A Wagner, Maximillian Rosario, Rizwan Romee, Melissa M Berrien-Elliott, Stephanie E Schneider, Jeffrey W Leong, Ryan P Sullivan, Brea A Jewell, Michelle Becker-Hapak, Timothy Schappe, Sara Abdel-Latif, Aaron R Ireland, Devika Jaishankar, Justin A King, Ravi Vij, Dennis Clement, Jodie Goodridge, Karl-Johan Malmberg, Hing C Wong, Todd A Fehniger
NK cells, lymphocytes of the innate immune system, are important for defense against infectious pathogens and cancer. Classically, the CD56dim NK cell subset is thought to mediate antitumor responses, whereas the CD56bright subset is involved in immunomodulation. Here, we challenge this paradigm by demonstrating that brief priming with IL-15 markedly enhanced the antitumor response of CD56bright NK cells. Priming improved multiple CD56bright cell functions: degranulation, cytotoxicity, and cytokine production...
October 3, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28954823/a-novel-intracellular-pool-of-lfa-1-is-critical-for-asymmetric-cd8-t-cell-activation-and-differentiation
#9
Tara Capece, Brandon L Walling, Kihong Lim, Kyun-Do Kim, Seyeon Bae, Hung-Li Chung, David J Topham, Minsoo Kim
The integrin lymphocyte function-associated antigen 1 (LFA-1; CD11a/CD18) is a key T cell adhesion receptor that mediates stable interactions with antigen-presenting cell (APC), as well as chemokine-mediated migration. Using our newly generated CD11a-mYFP knock-in mice, we discovered that naive CD8(+) T cells reserve a significant intracellular pool of LFA-1 in the uropod during migration. Intracellular LFA-1 quickly translocated to the cell surface with antigenic stimulus. Importantly, the redistribution of intracellular LFA-1 at the contact with APC was maintained during cell division and led to an unequal inheritance of LFA-1 in divided T cells...
November 6, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28945328/inactivated-sendai-virus-particles-upregulate-cancer-cell-icam-1-expression-with-enhancing-nk-cell-sensitivity-on-cancer-cell
#10
Simin Li, Tomoyuki Nishikawa, Yasufumi Kaneda
We have already reported that the inactivated Sendai virus (hemagglutinating virus of Japan; HVJ) envelope (HVJ-E) has multiple anti-cancer effects, including induction of cancer-selective cell death and activation of anti-cancer immunity. HVJ-E stimulates dendritic cells (DCs) to produce cytokines and chemokines such as IFN-β, IL-6, CCL5 and CXCL10, which activate both CD8(+) T cells and NK cells and recruit them to the tumor microenvironment. However, the effect of HVJ-E on modulating the sensitivity of cancer cells to immune cell attack has yet to be investigated...
September 25, 2017: Cancer Science
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
#11
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
#12
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
#13
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
#14
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...
September 6, 2017: ELife
https://www.readbyqxmd.com/read/28872666/active-dissemination-of-cellular-antigens-by-dcs-facilitates-cd8-t-cell-priming-in-lymph-nodes
#15
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 colocalization 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...
October 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
#16
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
#17
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...
December 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
#18
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...
October 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
#19
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
#20
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
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