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https://www.readbyqxmd.com/read/28550204/cutting-edge-origins-recruitment-and-regulation-of-cd11c-cells-in-inflamed-islets-of-autoimmune-diabetes-mice
#1
Joanna E Klementowicz, Ashley E Mahne, Allyson Spence, Vinh Nguyen, Ansuman T Satpathy, Kenneth M Murphy, Qizhi Tang
In NOD mice, CD11c(+) cells increase greatly with islet inflammation and contribute to autoimmune destruction of pancreatic β cells. In this study, we investigated their origin and mechanism of recruitment. CD11c(+) cells in inflamed islets resembled classical dendritic cells based on their transcriptional profile. However, the majority of these cells were not from the Zbtb46-dependent dendritic-cell lineage. Instead, monocyte precursors could give rise to CD11c(+) cells in inflamed islets. Chemokines Ccl5 and Ccl8 were persistently elevated in inflamed islets and the influx of CD11c(+) cells was partially dependent on their receptor Ccr5...
May 26, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28550203/socs1-is-a-key-molecule-that-prevents-regulatory-t-cell-plasticity-under-inflammatory-conditions
#2
Reiko Takahashi, Hiroko Nakatsukasa, Shunichi Shiozawa, Akihiko Yoshimura
We previously showed that regulatory T cells (Tregs) from T cell-specific Socs1-deficient mice (Socs1(fl/fl)Lck-Cre(+) mice) easily convert into Th1- or Th17-like cells (ex-Tregs), which lose Foxp3 expression and suppressive functions in vivo. Because Tregs in Socs1(fl/fl)Lck-Cre(+) mice are constantly exposed to a large amount of inflammatory cytokines produced by non-Tregs in vivo, in this study we analyzed Treg-specific Socs1-deficient mice (Socs1(fl/fl)Foxp3(YFP-Cre) mice). These mice developed dermatitis, splenomegaly, and lymphadenopathy that were much milder than those in Socs1(fl/fl)Lck-Cre(+) mice...
May 26, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28550202/antigen-specific-t-cell-analysis-reveals-that-active-immune-responses-to-%C3%AE-cell-antigens-are-focused-on-a-unique-set-of-epitopes
#3
Junbao Yang, Xiaomin Wen, Hengyu Xu, Nadia Torres-Chinn, Cate Speake, Carla J Greenbaum, Gerald T Nepom, William W Kwok
CD38 is an activation marker that is present on recently activated T cells, but absent on resting memory T cells. In this study, we show that CD45RO(+)CD38(+) β cell Ag-specific CD4(+) T cells were present at higher frequencies in type 1 diabetes subjects compared with those in healthy subjects. These results imply an ongoing β cell immunity years after onset of diabetes and suggest these activated T cells have an active role in the disease process. The Ag specificities of these activated T cells were determined by a novel CD154 T cell epitope mapping assay...
May 26, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28550190/patient-derived-anti-%C3%AE-2gp1-antibodies-recognize-a-peptide-motif-pattern-and-not-a-specific-sequence-of-residues
#4
Philippe de Moerloose, Céline Fickentscher, Françoise Boehlen, Jean-Marie Tiercy, Egbert K O Kruithof, Karim J Brandt
Antiphospholipid antibody syndrome is an autoimmune disease characterized by the presence of so-called antiphospholipid antibodies and clinical manifestations such as recurrent thromboembolic or pregnancy complications. Although the main antigenic determinant for antiphospholipid antibodies has been identified as the beta-2-glycoprotein 1 (β2GP1), the precise epitope recognized by antiphospholipid antibodies still remains largely unknown. In the present study, we wanted to identify a sequence in the domain I of β2GP1 able to induce the proliferation of CD4+ T cells isolated from antiphospholipid antibody syndrome patients but not from healthy donors and to interact with antiphospholipid antibodies...
May 26, 2017: Haematologica
https://www.readbyqxmd.com/read/28550183/somatic-mutation-spectrum-in-monoclonal-gammopathy-of-undetermined-significance-indicates-a-less-complex-genomic-landscape-compared-to-multiple-myeloma
#5
Aneta Mikulasova, Christopher P Wardell, Alexander Murison, Eileen M Boyle, Graham H Jackson, Jan Smetana, Zuzana Kufova, Ludek Pour, Viera Sandecka, Martina Almasi, Pavla Vsianska, Evzen Gregora, Petr Kuglik, Roman Hajek, Faith E Davies, Gareth J Morgan, Brian A Walker
Monoclonal gammopathy of undetermined significance (MGUS) is a premalignant precursor of multiple myeloma with a 1% risk of progression per year. Although targeted analyses have shown the presence of specific genetic abnormalities such as IGH translocations, RB1 deletion, 1q gain, hyperdiploidy or RAS genes mutations, little is known about the molecular mechanism of malignant transformation. We have performed whole exome sequencing together with CGH+SNP array analysis in 33 flow-cytometry separated abnormal plasma cell samples from MGUS patients to describe somatic gene mutations and chromosome changes at the genome-wide level...
May 26, 2017: Haematologica
https://www.readbyqxmd.com/read/28550117/comparative-exploration-of-multidimensional-flow-cytometry-software-a-model-approach-evaluating-t-cell-polyfunctional-behavior
#6
Timothy T Spear, Michael I Nishimura, Patricia E Simms
Advancement in flow cytometry reagents and instrumentation has allowed for simultaneous analysis of large numbers of lineage/functional immune cell markers. Highly complex datasets generated by polychromatic flow cytometry require proper analytical software to answer investigators' questions. A problem among many investigators and flow cytometry Shared Resource Laboratories (SRLs), including our own, is a lack of access to a flow cytometry-knowledgeable bioinformatics team, making it difficult to learn and choose appropriate analysis tool(s)...
May 26, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28550091/transgenic-expression-of-il15-improves-antiglioma-activity-of-il13ralpha2-car-t-cells-but-results-in-antigen-loss-variants
#7
Giedre Krenciute, Brooke L Prinzing, Zhongzhen Yi, Meng-Fen Wu, Hao Liu, Gianpietro Dotti, Irina V Balyasnikova, Stephen Gottschalk
Glioblastoma (GBM) is the most aggressive primary brain tumor in adults and is virtually incurable with conventional therapies. Immunotherapy with T cells expressing GBM-specific chimeric antigen receptors (CARs) is an attractive approach to improve outcomes. Although CAR T cells targeting GBM antigens such as IL13Ralpha2 (interleukin 13 Receptor Subunit Alpha 2), HER2 (human epidermal growth factor receptor 2), and EGFRvIII (epidermal growth factor receptor variant III) have had antitumor activity in preclinical models, early phase clinical testing has demonstrated limited antiglioma activity...
May 26, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28550052/distinct-chromatin-states-underlie-tumor-specific-t-cell-dysfunction
#8
(no author information available yet)
Tumor T cells differentiate through a plastic dysfunctional state and a fixed dysfunctional state.
May 26, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28549917/dendritic-cell-derived-exosomes-elicit-tumor-regression-in-autochthonous-hepatocellular-carcinoma-mouse-models
#9
Zhen Lu, Bingfeng Zuo, Renwei Jing, Xianjun Gao, Quan Rao, Zhili Liu, Han Qi, Hongxing Guo, HaiFang Yin
BACKGROUND & AIMS: Dendritic cell (DC)-derived exosomes (DEXs) form a new class of vaccines for cancer immunotherapy. However their potency in hepatocellular carcinoma (HCC), a life-threatening malignancy with limited treatment options in the clinic and responds poorly to immunotherapy, remains to be investigated. METHODS: Exosomes derived from α-fetoprotein (AFP) - expressing DCs (DEXAFP) were investigated in three different HCC mouse models systemically and tumor growth and microenvironment were monitored...
May 23, 2017: Journal of Hepatology
https://www.readbyqxmd.com/read/28549714/the-enigmatic-role-of-viruses-in-multiple-sclerosis-molecular-mimicry-or-disturbed-immune-surveillance
#10
REVIEW
Jens Geginat, Moira Paroni, Massimiliano Pagani, Daniela Galimberti, Raffaele De Francesco, Elio Scarpini, Sergio Abrignani
Multiple sclerosis (MS) is a T cell driven autoimmune disease of the central nervous system (CNS). Despite its association with Epstein-Barr Virus (EBV), how viral infections promote MS remains unclear. However, there is increasing evidence that the CNS is continuously surveyed by virus-specific T cells, which protect against reactivating neurotropic viruses. Here, we discuss how viral infections could lead to the breakdown of self-tolerance in genetically predisposed individuals, and how the reactivations of viruses in the CNS could induce the recruitment of both autoaggressive and virus-specific T cell subsets, causing relapses and progressive disability...
May 23, 2017: Trends in Immunology
https://www.readbyqxmd.com/read/28549586/critical-role-of-hla-dr%C3%AE-binding-peptides-peripheral-flanking-residues-in-fully-protective-malaria-vaccine-development
#11
César Reyes, Rocío Rojas-Luna, Jorge Aza-Conde, Luisa Tabares, Manuel A Patarroyo, Manuel E Patarroyo
A vaccine candidate component must fit perfectly into the antigen presenting HLA-DRβ* molecule's groove (or canonical nonapeptide) peptide binding region (PBR) during antigen presentation for proper presentation to the T-cell receptor (TCR), conforming a specific and stable macromolecular complex and induce an appropriate immune response. Antigen's peripheral flanking residues (PFR, positions (p) -p2 and p10) must thus establish strong interactions with the HLA-DRβ* - TCR complex. These amino acids (aa) have specific physico-chemical characteristics enabling differentiation between non-protective but antibody-inducer (NPAI), short-lived protection inducer (SLPI) and long-lasting protection inducer (LLPI) peptides when used as an antimalarial vaccine component...
May 23, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28549432/dendritic-cells-combined-with-tumor-cells-and-%C3%AE-galactosylceramide-induce-a-potent-therapeutic-and-nk-cell-dependent-antitumor-immunity-in-b-cell-lymphoma
#12
Laura Escribà-Garcia, Carmen Alvarez-Fernández, Marta Tellez-Gabriel, Jorge Sierra, Javier Briones
BACKGROUND: Invariant natural killer T (iNKT) cells are a small population of lymphocytes with unique specificity for glycolipid antigens presented by non-polymorphic CD1d receptor on dendritic cells (DCs). iNKT cells play a central role in tumor immunology since they are implicated in the coordination of innate and adaptive immune responses. These cells can be activated with the prototypic lipid α-galactosylceramide (α-GalCer), stimulating interferon gamma (IFN-γ) production and cytokine secretion, which contribute to the enhancement of T cell activation...
May 26, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28549148/risk-factors-for-invasive-fungal-disease-in-pediatric-cancer-and-hematopoietic-stem-cell-transplantation-a-systematic-review
#13
Brian T Fisher, Paula D Robinson, Thomas Lehrnbecher, William J Steinbach, Theoklis E Zaoutis, Bob Phillips, Lillian Sung
Background.: Although a number of risk factors have been associated with invasive fungal disease (IFD), a systematic review of the literature to document pediatric-specific factors has not been performed. Methods.: We used the Ovid SP platform to search Medline, Medline In-Process, and Embase for studies that identified risk factors for IFD in children with cancer or those who undergo hematopoietic stem cell transplantation (HSCT). We included studies if they consisted of children or adolescents (<25 years) who were receiving treatment for cancer or undergoing HSCT and if the study evaluated risk factors among patients with and those without IFD...
May 26, 2017: Journal of the Pediatric Infectious Diseases Society
https://www.readbyqxmd.com/read/28549038/use-of-smooth-muscle-myosin-heavy-chain-as-an-effective-marker-of-follicular-dendritic-cells
#14
Ioannis Ioannidis, Javier A Laurini
Smooth muscle myosin heavy chain (SMMHC) is a major structural component of the contractile apparatus in smooth muscle cells. Even though it is considered a relatively specific marker for terminal smooth muscle cell differentiation, expression in other cell types such as follicular dendritic cells (FDCs) has rarely been reported. To determine whether SMMHC represents an effective FDC marker in lymphoid tissues, we compared the immunohistochemical results for SMMHC with those of the traditional FDC markers podoplanin (D2-40) and CD21...
May 25, 2017: Applied Immunohistochemistry & Molecular Morphology: AIMM
https://www.readbyqxmd.com/read/28548942/the-n-terminal-tail-coordinates-with-carbohydrate-recognition-domain-to-mediate-galectin-3-induced-apoptosis-in-t-cells
#15
Huiting Xue, Lu Liu, Zihan Zhao, Zhongyu Zhang, Yuan Guan, Hairong Cheng, Yifa Zhou, Guihua Tai
Galectin-3 is a galectin with a unique flexible N-terminal tail (NT) connected to the conserved carbohydrate recognition domain (CRD). Galectin-3 is associated with tumor immune tolerance and exhibits an ability to induce T cell apoptosis. We used Jurkat, Jurkat E6-1 and CEM T-cell lines and human peripheral blood mononuclear cells (PBMCs) to investigate the specific roles of the CRD and NT in inducing T cell apoptosis. Galectin-3 triggered sustained extracellular signal-regulated kinase (ERK) phosphorylation that induced apoptosis...
May 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/28548834/subtly-modulating-glycogen-synthase-kinase-3-%C3%AE-allosteric-inhibitors-development-and-their-potential-for-the-treatment-of-chronic-diseases
#16
Valle Palomo, Daniel I Pérez, Carlos Roca, Cara Anderson, Natalia Rodriguez-Muela, Concepción Pérez, Jose A Morales-Garcia, Julio A Reyes, Nuria E Campillo, Ana M Pérez-Castillo, Lee L Rubin, Lubov T Timchenko, Carmen Gil, Ana Martínez
Glycogen synthase kinase 3 β (GSK-3β) is a central target in several unmet diseases. To increase the specificity of GSK-3β inhibitors in chronic treatments we are developing small molecules allowing subtle modulation of GSK-3β activity. Design synthesis, structure-activity relationships and binding mode of quinoline-3-carbohydrazide derivatives as allosteric modulators of GSK-3β are here presented. Furthermore, we show how allosteric binders may overcome the β-catenin side effects associated to strong GSK-3β inhibition...
May 26, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28548677/destabilization-of-human-insulin-fibrils-by-peptides-of-fruit-bromelain-derived-from-ananas-comosus-pineapple
#17
Sromona Das, Debasish Bhattacharyya
Deposition of insulin aggregates in human body leads to dysfunctioning of several organs. Effectiveness of fruit bromelain from pineapple in prevention of insulin aggregate was investigated. Proteolyses of bromelain was done as par human digestive system and the pool of small peptides was separated from larger peptides and proteins. Under conditions of growth of insulin aggregates from its monomers, this pool of peptides restricted the reaction upto formation of oligomers of limited size. These peptides also destabilized preformed insulin aggregates to oligomers...
May 26, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28548645/waldenstrom-macroglobulinemia-cells-devoid-of-btk-c481s-or-cxcr4-whim-like-mutations-acquire-resistance-to-ibrutinib-through-upregulation-of-bcl-2-and-akt-resulting-in-vulnerability-towards-venetoclax-or-mk2206-treatment
#18
A Paulus, S Akhtar, H Yousaf, A Manna, S M Paulus, Y Bashir, T R Caulfield, M Kuranz-Blake, K Chitta, X Wang, Y Asmann, R Hudec, W Springer, S Ailawadhi, A Chanan-Khan
Although ibrutinib is highly effective in Waldenstrom macroglobulinemia (WM), no complete remissions in WM patients treated with ibrutinib have been reported to date. Moreover, ibrutinib-resistant disease is being steadily reported and is associated with dismal clinical outcome (overall survival of 2.9-3.1 months). To understand mechanisms of ibrutinib resistance in WM, we established ibrutinib-resistant in vitro models using validated WM cell lines. Characterization of these models revealed the absence of BTK(C481S) and CXCR4(WHIM-like) mutations...
May 26, 2017: Blood Cancer Journal
https://www.readbyqxmd.com/read/28548103/an-aavp-based-solid-phase-transducing-matrix-for-transgene-delivery-potential-for-translational-applications
#19
T L Smith, G R Souza, R L Sidman, W Arap, R Pasqualini
A hybrid vector of adeno-associated virus and phage (termed AAVP) has been introduced as a platform for systemic ligand-directed delivery of transgenes to tumors over the past decade. A series of studies have evaluated the AAVP platform for potential theranostic or purely therapeutic applications in several tumor models. Sufficient ligand-directed tumor targeting consistently resulted in specific molecular-genetic imaging and/or anti-tumor responses to 'suicide' transgene delivery. However, efforts to optimize transduction efficiency are still ongoing...
May 26, 2017: Cancer Gene Therapy
https://www.readbyqxmd.com/read/28548102/replicating-viral-vector-platform-exploits-alarmin-signals-for-potent-cd8-t-cell-mediated-tumour-immunotherapy
#20
Sandra M Kallert, Stephanie Darbre, Weldy V Bonilla, Mario Kreutzfeldt, Nicolas Page, Philipp Müller, Matthias Kreuzaler, Min Lu, Stéphanie Favre, Florian Kreppel, Max Löhning, Sanjiv A Luther, Alfred Zippelius, Doron Merkler, Daniel D Pinschewer
Viral infections lead to alarmin release and elicit potent cytotoxic effector T lymphocyte (CTL(eff)) responses. Conversely, the induction of protective tumour-specific CTL(eff) and their recruitment into the tumour remain challenging tasks. Here we show that lymphocytic choriomeningitis virus (LCMV) can be engineered to serve as a replication competent, stably-attenuated immunotherapy vector (artLCMV). artLCMV delivers tumour-associated antigens to dendritic cells for efficient CTL priming. Unlike replication-deficient vectors, artLCMV targets also lymphoid tissue stroma cells expressing the alarmin interleukin-33...
May 26, 2017: Nature Communications
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