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https://www.readbyqxmd.com/read/28319073/ex-vivo-t-cell-depletion-in-allogeneic-hematopoietic-stem-cell-transplant-past-present-and-future
#1
REVIEW
A Saad, L S Lamb
The most common cause of post-transplant mortality in patients with hematological malignancy is relapse, followed by GvHD, infections, organ toxicity and second malignancy. Immune-mediated complications such as GvHD continue to be challenging, yet amenable to control through manipulation of the T-cell compartment of the donor graft with subsequent immunomodulation after transplant. However, risk of both relapse and infection increase concomitantly with T-cell depletion (TCD) strategies that impair immune recovery...
March 20, 2017: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/28318492/-brain-tumor-immunotherapy-illusion-or-hope
#2
REVIEW
Denis Migliorini, Valérie Dutoit, Paul R Walker, Pierre-Yves Dietrich
Immunotherapy has proven efficient for many tumors and is now part of standard of care in many indications. What is the picture for brain tumors? The recent development of anti-CTLA-4 and PD1 immune checkpoint inhibitors, which have the ability to restore T lymphocytes activity, has gathered enthusiasm and is now paving the way towards more complex models of immune system manipulation. These models include, among others, vaccination and adoptive T cell transfer technologies. Complementary to those strategies, molecules capable of reshaping the immune tumor microenvironment are currently being investigated in early phase trials...
March 16, 2017: Bulletin du Cancer
https://www.readbyqxmd.com/read/28302860/mobile-mute-specifies-subsidiary-cells-to-build-physiologically-improved-grass-stomata
#3
Michael T Raissig, Juliana L Matos, M Ximena Anleu Gil, Ari Kornfeld, Akhila Bettadapur, Emily Abrash, Hannah R Allison, Grayson Badgley, John P Vogel, Joseph A Berry, Dominique C Bergmann
Plants optimize carbon assimilation while limiting water loss by adjusting stomatal aperture. In grasses, a developmental innovation-the addition of subsidiary cells (SCs) flanking two dumbbell-shaped guard cells (GCs)-is linked to improved stomatal physiology. Here, we identify a transcription factor necessary and sufficient for SC formation in the wheat relative Brachypodium distachyon. Unexpectedly, the transcription factor is an ortholog of the stomatal regulator AtMUTE, which defines GC precursor fate in Arabidopsis The novel role of BdMUTE in specifying lateral SCs appears linked to its acquisition of cell-to-cell mobility in Brachypodium Physiological analyses on SC-less plants experimentally support classic hypotheses that SCs permit greater stomatal responsiveness and larger range of pore apertures...
March 17, 2017: Science
https://www.readbyqxmd.com/read/28302753/erythropoietin-receptor-mediated-molecular-crosstalk-promotes-t-cell-immunoregulation-and-transplant-survival
#4
Carolina Purroy, Robert L Fairchild, Toshiaki Tanaka, William M Baldwin, Joaquin Manrique, Joren C Madsen, Robert B Colvin, Alessandro Alessandrini, Bruce R Blazar, Miguel Fribourg, Chiara Donadei, Umberto Maggiore, Peter S Heeger, Paolo Cravedi
Although spontaneous kidney transplant acceptance/tolerance occurs in mice and occasionally in humans, mechanisms remain unclear. Herein we test the hypothesis that EPO, a hormone predominantly produced by the adult kidney, has immunomodulating properties that are required for spontaneous kidney graft acceptance. In vitro, in a manner dependent on the EPO receptor and CD131 on antigen-presenting cells, EPO induced the secretion of active TGFβ by antigen-presenting cells, which in turn converted naïve CD4(+) T cells into functional Foxp3(+) regulatory T cells (Treg)...
March 16, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28296000/novel-application-of-localized-nanodelivery-of-anti-il6-protects-organ-transplant-from-ischemia-reperfusion-injuries
#5
Zhabiz Solhjou, Mayuko Uehara, Baharak Bahmani, Omar H Maarouf, Takaharu Ichimura, Craig R Brooks, Wanlong Xu, Mine Yilmaz, Abdala Elkhal, Stefan G Tullius, Indira Guleria, Martina McGrath, Reza Abdi
Ischemia reperfusion injury (IRI) evokes intra-graft inflammatory responses, which markedly augment alloimmune responses against the graft. Understanding the mechanisms underlying these responses is fundamental to develop therapeutic regimens to prevent/ameliorate organ IRI. Here, we demonstrate that IRI results in a marked increase in mitochondrial damage and autophagy in dendritic cells (DC). While autophagy is a survival mechanism for ischemic DC, it also augments their production of IL6. Allograft derived dendritic cells (ADDC) lacking autophagy related gene 5 (Atg5) showed higher death rates post-transplantation...
March 12, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28290557/ectopic-expression-of-arabidopsis-fd-and-fd-paralogue-in-rice-results-in-dwarfism-with-size-reduction-of-spikelets
#6
Seonghoe Jang, Hsing-Yi Li, Mei-Lin Kuo
Key flowering genes, FD and FD PARALOGUE (FDP) encoding bZIP transcription factors that interact with a FLOWERING LOCUS T (FT) in Arabidopsis were ectopically expressed in rice since we found AtFD and AtFDP also interact with HEADING DATE 3a (Hd3a) and RICE FLOWERING LOCUS T 1 (RFT1). Transgenic rice plants overexpressing AtFD and AtFDP caused reduction in plant height and spikelet size with decreased expression of genes involved in cell elongation without significant flowering time alteration in spite of increased expression of OsMADS14 and OsMADS15, rice homologues of APETALA1 (AP1) in the leaves...
March 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28289977/location-function-and-ontogeny-of-pulmonary-macrophages-during-the-steady-state
#7
REVIEW
Natalio Garbi, Bart N Lambrecht
The lung is continuously exposed to potentially hazardous environmental challenges in the form of inert material and microbes. Pulmonary macrophages are critical in maintaining a low inflammatory context in the lung to facilitate optimal gas exchange. During infection, however, they mediate the immediate response to invading microorganisms in coordination with epithelial cells and other tissue-resident immune cells including dendritic cells, innate lymphocytes and memory T cells, and pulmonary interstitial macrophages...
March 13, 2017: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/28289147/gfpuv-expressing-recombinant-rickettsia-typhi-a-useful-tool-for-the-study-of-pathogenesis-and-cd8-t-cell-immunology-in-rickettsia-typhi-infection
#8
Matthias Hauptmann, Nicole Burkhardt, Ulrike Munderloh, Svenja Kuehl, Ulricke Richardt, Susanne Krasemann, Kristin Hartmann, Till Krech, Bernhard Fleischer, Christian Keller, Anke Osterloh
Rickettsia (R) typhi is the causative agent of endemic typhus, a disease that occurs wordwide with increasing incidence and can be fatal. Because of its obligate intracellular life style, genetic manipulation of this pathogen is difficult. Nonetheless, in recent years genetic manipulation tools have been successfully applied to rickettsiae. We describe here for the first time the transformation of R. typhi with the pRAM18dRGA plasmid that originally derives from R. amblyommatis and encodes for the expression of GFP(uv) Transformed R...
March 13, 2017: Infection and Immunity
https://www.readbyqxmd.com/read/28287116/photothermally-triggered-actuation-of-hybrid-materials-as-a-new-platform-for-in-vitro-cell-manipulation
#9
Amy Sutton, Tanya Shirman, Jaakko V I Timonen, Grant T England, Philseok Kim, Mathias Kolle, Thomas Ferrante, Lauren D Zarzar, Elizabeth Strong, Joanna Aizenberg
Mechanical forces in the cell's natural environment have a crucial impact on growth, differentiation and behaviour. Few areas of biology can be understood without taking into account how both individual cells and cell networks sense and transduce physical stresses. However, the field is currently held back by the limitations of the available methods to apply physiologically relevant stress profiles on cells, particularly with sub-cellular resolution, in controlled in vitro experiments. Here we report a new type of active cell culture material that allows highly localized, directional and reversible deformation of the cell growth substrate, with control at scales ranging from the entire surface to the subcellular, and response times on the order of seconds...
March 13, 2017: Nature Communications
https://www.readbyqxmd.com/read/28284079/label-free-identification-of-activated-t-lymphocytes-through-tridimensional-microsensors-on-chip
#10
Enrica Rollo, Enrico Tenaglia, Raphaël Genolet, Elena Bianchi, Alexandre Harari, George Coukos, Carlotta Guiducci
Label-free approaches to assess cell properties ideally suit the requirements of cell-based therapeutics, since they permit to characterize cells with minimal perturbation and manipulation, at the benefit of sample recovery and re-employment for treatment. For this reason, label-free techniques would find sensible application in adoptive T cell-based immunotherapy. In this work, we describe the label-free and single-cell detection of in vitro activated T lymphocytes in flow through an electrical impedance-based setup...
March 3, 2017: Biosensors & Bioelectronics
https://www.readbyqxmd.com/read/28280061/purinergic-receptor-transactivation-by-the-%C3%AE-2-adrenergic-receptor-increases-intracellular-ca-2-in-non-excitable-cells
#11
Wayne Stallaert, Emma T van der Westhuizen, Anne-Marie Schonegge, Bianca Plouffe, Mireille Hogue, Viktoria Lukashova, Asuka Inoue, Satoru Ishida, Junken Aoki, Christian Le Gouill, Michel Bouvier
The β2 adrenergic receptor (β2AR) increases intracellular Ca(2+) in a variety of cell types. By combining pharmacological and genetic manipulations, we reveal a novel mechanism through which the β2AR promotes Ca(2+) mobilization (pEC50 = 7.32 ± 0.10) in non-excitable human embryonic kidney (HEK)-293S cells. Down-regulation of Gs with sustained cholera toxin pre-treatment and the use Gs-null HEK293 (ΔGs-HEK293) cells generated using the CRISPR/Cas9 system, combined with pharmacological modulation of cAMP formation revealed a Gs-dependent but cAMP-independent increase in intracellular Ca(2+) following β2AR stimulation...
March 9, 2017: Molecular Pharmacology
https://www.readbyqxmd.com/read/28279813/the-role-of-chemokines-in-hypertension-and-consequent-target-organ-damage
#12
REVIEW
Nathan P Rudemiller, Steven D Crowley
Immune cells infiltrate the kidney, vasculature, and central nervous system during hypertension, consequently amplifying tissue damage and/or blood pressure elevation. Mononuclear cell motility depends partly on chemokines, which are small cytokines that guide cells through an increasing concentration gradient via ligation of their receptors. Tissue expression of several chemokines is elevated in clinical and experimental hypertension. Likewise, immune cells have enhanced chemokine receptor expression during hypertension, driving immune cell infiltration and inappropriate inflammation in cardiovascular control centers...
March 6, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28273064/class-iia-hdac-inhibition-reduces-breast-tumours-and-metastases-through-anti-tumour-macrophages
#13
Jennifer L Guerriero, Alaba Sotayo, Holly E Ponichtera, Jessica A Castrillon, Alexandra L Pourzia, Sara Schad, Shawn F Johnson, Ruben D Carrasco, Suzan Lazo, Roderick T Bronson, Scott P Davis, Mercedes Lobera, Michael A Nolan, Anthony Letai
Although the main focus of immuno-oncology has been manipulating the adaptive immune system, harnessing both the innate and adaptive arms of the immune system might produce superior tumour reduction and elimination. Tumour-associated macrophages often have net pro-tumour effects, but their embedded location and their untapped potential provide impetus to discover strategies to turn them against tumours. Strategies that deplete (anti-CSF-1 antibodies and CSF-1R inhibition) or stimulate (agonistic anti-CD40 or inhibitory anti-CD47 antibodies) tumour-associated macrophages have had some success...
March 8, 2017: Nature
https://www.readbyqxmd.com/read/28265270/borrelia-burgdorferi-manipulates-innate-and-adaptive-immunity-to-establish-persistence-in-rodent-reservoir-hosts
#14
REVIEW
Karen E Tracy, Nicole Baumgarth
Borrelia burgdorferi sensu lato species complex is capable of establishing persistent infections in a wide variety of species, particularly rodents. Infection is asymptomatic or mild in most reservoir host species, indicating successful co-evolution of the pathogen with its natural hosts. However, infected humans and other incidental hosts can develop Lyme disease, a serious inflammatory syndrome characterized by tissue inflammation of joints, heart, muscles, skin, and CNS. Although B. burgdorferi infection induces both innate and adaptive immune responses, they are ultimately ineffective in clearing the infection from reservoir hosts, leading to bacterial persistence...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28261211/targeting-the-monocyte-macrophage-lineage-in-solid-organ-transplantation
#15
REVIEW
Thierry P P van den Bosch, Nynke M Kannegieter, Dennis A Hesselink, Carla C Baan, Ajda T Rowshani
There is an unmet clinical need for immunotherapeutic strategies that specifically target the active immune cells participating in the process of rejection after solid organ transplantation. The monocyte-macrophage cell lineage is increasingly recognized as a major player in acute and chronic allograft immunopathology. The dominant presence of cells of this lineage in rejecting allograft tissue is associated with worse graft function and survival. Monocytes and macrophages contribute to alloimmunity via diverse pathways: antigen processing and presentation, costimulation, pro-inflammatory cytokine production, and tissue repair...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28258702/advances-in-targeting-co-inhibitory-and-co-stimulatory-pathways-in-transplantation-settings-the-yin-to-the-yang-of%C3%A2-cancer-immunotherapy
#16
REVIEW
Leslie S Kean, Laurence A Turka, Bruce R Blazar
In the past decade, the power of harnessing T-cell co-signaling pathways has become increasingly understood to have significant clinical importance. In cancer immunotherapy, the field has concentrated on two related modalities: First, targeting cancer antigens through highly activated chimeric antigen T cells (CAR-Ts) and second, re-animating endogenous quiescent T cells through checkpoint blockade. In each of these strategies, the therapeutic goal is to re-ignite T-cell immunity, in order to eradicate tumors...
March 2017: Immunological Reviews
https://www.readbyqxmd.com/read/28255696/reconstitution-of-tcr-signaling-using-supported-lipid-bilayers
#17
Xiaolei Su, Jonathon A Ditlev, Michael K Rosen, Ronald D Vale
Biochemical reconstitution has served as an important tool for understanding the mechanisms of many cellular processes including DNA replication, transcription, translation, vesicle trafficking, and ubiquitin-mediated proteolysis. Here, we demonstrate that biochemical reconstitution can be applied to studying a complex signaling pathway involving as many as 12 proteins or protein complexes acting at the surface of model membranes. We show that a temporal sequence of events in activated T cells beginning with phosphorylation of the T cell receptor and culminating in the activation of actin polymerization can be replicated in vitro...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28255268/regulatory-axis-of-mir-195-497-and-hmga1-id3-governs-muscle-cell-proliferation-and-differentiation
#18
Huiling Qiu, Jiasheng Zhong, Lan Luo, Zhixiong Tang, Nian Liu, Kang Kang, Li Li, Deming Gou
Myocytes withdraw from the cell cycle to differentiate during muscle development. Given the capacity of microRNAs (miRNAs) to regulate gene expression during development, we screened for miRNAs that were associated with muscle development. S-Poly(T) Plus analysis of 273 miRNAs in porcine longissimus dorsi muscles revealed 14 miRNAs that were strongly upregulated with age of postnatal muscle development in vivo, including miR-195 and miR-497. These two miRNAs were also strongly upregulated at late differentiation stages of mouse skeletal myoblast C2C12 cells, and demethylation treatment induced significant upregulation of miR-195/497...
2017: International Journal of Biological Sciences
https://www.readbyqxmd.com/read/28252650/amino-acid-transporters-in-t-cell-activation-and-differentiation
#19
REVIEW
W Ren, G Liu, J Yin, B Tan, G Wu, F W Bazer, Y Peng, Y Yin
T-cell-mediated immune responses aim to protect mammals against cancers and infections, and are also involved in the pathogenesis of various inflammatory or autoimmune diseases. Cellular uptake and the utilization of nutrients is closely related to the T-cell fate decision and function. Research in this area has yielded surprising findings in the importance of amino-acid transporters for T-cell development, homeostasis, activation, differentiation and memory. In this review, we present current information on amino-acid transporters, such as LAT1 (l-leucine transporter), ASCT2 (l-glutamine transporter) and GAT-1 (γ-aminobutyric acid transporter-1), which are critically important for mediating peripheral naive T-cell homeostasis, activation and differentiation, especially for Th1 and Th17 cells, and even memory T cells...
March 2, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28252135/t-cell-immunoengineering-with-advanced-biomaterials
#20
Derfogail Delcassian, Susanne Sattler, Iain E Dunlop
Recent advances in biomaterials design offer the potential to actively control immune cell activation and behaviour. Many human diseases, such as infections, cancer, and autoimmune disorders, are partly mediated by inappropriate or insufficient activation of the immune system. T cells play a central role in the host immune response to these diseases, and so constitute a promising cell type for manipulation. In vivo, T cells are stimulated by antigen presenting cells (APC), therefore to design immunoengineering biomaterials that control T cell behaviour, artificial interfaces that mimic the natural APC-T cell interaction are required...
March 1, 2017: Integrative Biology: Quantitative Biosciences From Nano to Macro
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