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https://www.readbyqxmd.com/read/27936218/a-key-role-for-inhibins-in-dendritic-cell-maturation-and-function
#1
Roxana Olguín-Alor, Marisol de la Fuente-Granada, Laura C Bonifaz, Laura Antonio-Herrera, Eduardo A García-Zepeda, Gloria Soldevila
Inhibins are members of the TGFβ superfamily, which regulate many cellular processes including differentiation, proliferation, survival and apoptosis. Although initially described as hormones regulating the hypothalamus-pituitary-gonadal axis, based on their ability to antagonize Activins, our group has recently reported that they play a role in thymocyte differentiation and survival, as well as in thymic stromal cell maturation and nTreg generation. Here, we used Inhibin knock out mice (Inhα-/-) to investigate the role of Inhibins in peripheral dendritic cell maturation and function...
2016: PloS One
https://www.readbyqxmd.com/read/27936167/the-slavic-nbn-founder-mutation-a-role-for-reproductive-fitness
#2
Eva Seemanova, Raymonda Varon, Jan Vejvalka, Petr Jarolim, Pavel Seeman, Krystyna H Chrzanowska, Martin Digweed, Igor Resnick, Ivo Kremensky, Kathrin Saar, Katrin Hoffmann, Véronique Dutrannoy, Mohsen Karbasiyan, Mehdi Ghani, Ivo Barić, Mustafa Tekin, Peter Kovacs, Michael Krawczak, André Reis, Karl Sperling, Michael Nothnagel
The vast majority of patients with Nijmegen Breakage Syndrome (NBS) are of Slavic origin and carry a deleterious deletion (c.657del5; rs587776650) in the NBN gene on chromosome 8q21. This mutation is essentially confined to Slavic populations and may thus be considered a Slavic founder mutation. Notably, not a single parenthood of a homozygous c.657del5 carrier has been reported to date, while heterozygous carriers do reproduce but have an increased cancer risk. These observations seem to conflict with the considerable carrier frequency of c...
2016: PloS One
https://www.readbyqxmd.com/read/27936058/modeling-the-role-of-lanthionine-synthetase-c-like-2-lancl2-in-the-modulation-of-immune-responses-to-helicobacter-pylori-infection
#3
Andrew Leber, Josep Bassaganya-Riera, Nuria Tubau-Juni, Victoria Zoccoli-Rodriguez, Monica Viladomiu, Vida Abedi, Pinyi Lu, Raquel Hontecillas
Immune responses to Helicobacter pylori are orchestrated through complex balances of host-bacterial interactions, including inflammatory and regulatory immune responses across scales that can lead to the development of the gastric disease or the promotion of beneficial systemic effects. While inflammation in response to the bacterium has been reasonably characterized, the regulatory pathways that contribute to preventing inflammatory events during H. pylori infection are incompletely understood. To aid in this effort, we have generated a computational model incorporating recent developments in the understanding of H...
2016: PloS One
https://www.readbyqxmd.com/read/27935917/safety-and-efficacy-of-azathioprine-as-a-second-line-therapy-for-primary-immune-thrombocytopenic-purpura
#4
B S Poudyal, B Sapkota, G S Shrestha, S Thapalia, B Gyawali, S Tuladhar
INTRODUCTION: Immune thrombocytopenic purpura remains common blood disease in Nepal. Azathioprine is an oral immunosupressive medicine which has been used widely in various autoimmune disease and solid organ transplant patients. It is inexpensive, easily available and well tolerated medicine. This study was carried out to evaluate efficacy and safety of azathioprine as a second line medicine for primary ITP patients who were refractory to steroid therapy. METHODS: The observational, pre-post study was conducted at Government of Nepal Civil Service Hospital, Kathmandu from January to October 2014...
July 2016: JNMA; Journal of the Nepal Medical Association
https://www.readbyqxmd.com/read/27935476/assessing-the-mechanism-and-therapeutic-potential-of-modulators-of-the-human-mediator-complex-associated-protein-kinases
#5
Paul Andrew Clarke, Maria-Jesus Ortiz-Ruiz, Robert TePoele, Olajumoke Adeniji-Popoola, Gary Box, Will Court, Stefanie Czasch, Samer El Bawab, Christina Esdar, Ken Ewan, Sharon Gowan, Alexis De Haven Brandon, Phllip Hewitt, Stephen M Hobbs, Wolfgang Kaufmann, Aurélie Mallinger, Florence Raynaud, Toby Roe, Felix Rohdich, Kai Schiemann, Stephanie Simon, Richard Schneider, Melanie Valenti, Stefan Weigt, Julian Blagg, Andree Blaukat, Trevor C Dale, Suzanne A Eccles, Stefan Hecht, Klaus Urbahns, Paul Workman, Dirk Wienke
Mediator-associated kinases CDK8/19 are context-dependent drivers or suppressors of tumorigenesis. Their inhibition is predicted to have pleiotropic effects, but it is unclear whether this will impact on the clinical utility of CDK8/19 inhibitors. We discovered two series of potent chemical probes with high selectivity for CDK8/19. Despite pharmacodynamic evidence for robust on-target activity, the compounds exhibited modest, though significant, efficacy against human tumor lines and patient-derived xenografts...
December 9, 2016: ELife
https://www.readbyqxmd.com/read/27933701/ccr2-mediates-helicobacter-pylori-induced-immune-tolerance-and-contributes-to-mucosal-homeostasis
#6
Xia Sun, Min Zhang, Mohamad El-Zaatari, Gray B Huffnagle, John Y Kao
BACKGROUND: We previously demonstrated that H. pylori infection leads to increased induction of regulatory T cells in local and systemic immune compartments. Here, we investigate the role of CCR2 in the tolerogenic programing of dendritic cells in a mouse model of H. pylori infection. MATERIALS AND METHODS: CCR2 deficient (CCR2KO) mice and wild-type (Wt) mice infected with H. pylori SS1 strain were analyzed by qPCR and FACS analysis. In vitro, bone marrow-derived DC on day 6 from CCR2KO and Wt mice cocultured with or without H...
December 8, 2016: Helicobacter
https://www.readbyqxmd.com/read/27933315/immunogenicity-of-self-tumor-associated-proteins-is-enhanced-through-protein-truncation
#7
Tim Kottke, Kevin G Shim, Vanesa Alonso-Camino, Shane Zaidi, Rosa Maria Diaz, Jose Pulido, Jill Thompson, Karishma R Rajani, Laura Evgin, Elizabeth Ilett, Hardev Pandha, Kevin Harrington, Peter Selby, Alan Melcher, Richard Vile
We showed previously that therapy with Vesicular Stomatitis Virus (VSV) expressing tumor-associated proteins eradicates established tumors. We show here that when cellular cDNA were cloned into VSV which retained their own poly-A signal, viral species emerged in culture which had deleted the cellular poly-A signal and also contained a truncated form of the protein coding sequence. Typically, the truncation occurred such that a Tyrosine-encoding codon was converted into a STOP codon. We believe that the truncation of tumor-associated proteins expressed from VSV in this way occurred to preserve the ability of the virus to replicate efficiently...
2016: Molecular Therapy Oncolytics
https://www.readbyqxmd.com/read/27933310/dynamics-of-antigen-presentation-to-transgene-product-specific-cd4-t-cells-and-of-treg-induction-upon-hepatic-aav-gene-transfer
#8
George Q Perrin, Irene Zolotukhin, Alexandra Sherman, Moanaro Biswas, Ype P de Jong, Cox Terhorst, Andrew M Davidoff, Roland W Herzog
The tolerogenic hepatic microenvironment impedes clearance of viral infections but is an advantage in viral vector gene transfer, which often results in immune tolerance induction to transgene products. Although the underlying tolerance mechanism has been extensively studied, our understanding of antigen presentation to transgene product-specific CD4(+) T cells remains limited. To address this, we administered hepatotropic adeno-associated virus (AAV8) vector expressing cytoplasmic ovalbumin (OVA) into wt mice followed by adoptive transfer of transgenic OVA-specific T cells...
2016: Molecular Therapy. Methods & Clinical Development
https://www.readbyqxmd.com/read/27933275/an-in-vitro-co-culture-mouse-model-demonstrates-efficient-vaccine-mediated-control-of-francisella-tularensis-schu-s4-and-identifies-nitric-oxide-as-a-predictor-of-efficacy
#9
Igor Golovliov, Helena Lindgren, Kjell Eneslätt, Wayne Conlan, Amandine Mosnier, Thomas Henry, Anders Sjöstedt
Francisella tularensis is a highly virulent intracellular bacterium and cell-mediated immunity is critical for protection, but mechanisms of protection against highly virulent variants, such as the prototypic strain F. tularensis strain SCHU S4, are poorly understood. To this end, we established a co-culture system, based on splenocytes from naïve, or immunized mice and in vitro infected bone marrow-derived macrophages that allowed assessment of mechanisms controlling infection with F. tularensis. We utilized the system to understand why the clpB gene deletion mutant, ΔclpB, of SCHU S4 shows superior efficacy as a vaccine in the mouse model as compared to the existing human vaccine, the live vaccine strain (LVS)...
2016: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/27933042/the-role-of-stress-and-stress-adaptations-in-determining-the-fate-of-the-bacterial-pathogen-listeria-monocytogenes-in-the-food-chain
#10
REVIEW
Kerrie NicAogáin, Conor P O'Byrne
The foodborne pathogen Listeria monocytogenes is a highly adaptable organism that can persist in a wide range of environmental and food-related niches. The consumption of contaminated ready-to-eat foods can cause infections, termed listeriosis, in vulnerable humans, particularly those with weakened immune systems. Although these infections are comparatively rare they are associated with high mortality rates and therefore this pathogen has a significant impact on food safety. L. monocytogenes can adapt to and survive a wide range of stress conditions including low pH, low water activity, and low temperature, which makes it problematic for food producers who rely on these stresses for preservation...
2016: Frontiers in Microbiology
https://www.readbyqxmd.com/read/27932423/integrated-genomic-analysis-of-survival-outliers-in-glioblastoma
#11
Sen Peng, Harshil Dhurv, Brock Armstrong, Bodour Salhia, Christophe Legendre, Jeffrey Kiefer, Julianna Parks, Selene Virk, Andrew E Sloan, Quinn T Ostrom, Jill S Barnholtz-Sloan, Nhan L Tran, Michael E Berens
BACKGROUND: To elucidate molecular features associated with disproportionate survival of glioblastoma (GB) patients, we conducted deep genomic comparative analysis of a cohort of patients receiving standard therapy (surgery plus concurrent radiation and temozolomide); "GB outliers" were identified: long-term survivor of 33 months (LTS; n = 8) versus short-term survivor of 7 months (STS; n = 10). METHODS: We implemented exome, RNA, whole genome sequencing, and DNA methylation for collection of deep genomic data from STS and LTS GB patients...
December 8, 2016: Neuro-oncology
https://www.readbyqxmd.com/read/27932123/serum-levels-of-interleukin-34-during-acute-rejection-in-liver-transplantation
#12
D San Segundo, P Ruiz, J Irure, M T Arias-Loste, A Cuadrado, A Puente, F Casafont, M López-Hoyos, J Crespo, E Fábrega
INTRODUCTION: Accumulating evidence indicates that interleukin (IL)-34 participates in T-cell homeostasis and tolerance due to the ability of IL-34 to trigger apoptosis of Th1, Th17, and Tc1 cells, but spare Th2 cells and Treg. In addition, IL-34 exerts anti-inflammatory effects by impairing leukocyte adhesion and transendothelial migration, and reducing the secretion of proinflammatory cytokines. The aim of our study was to investigate the time course of serum levels of IL-34 during hepatic allograft rejection...
November 2016: Transplantation Proceedings
https://www.readbyqxmd.com/read/27931844/dendritic-cells-in-hematological-malignancies
#13
REVIEW
Domenico Galati, Gaetano Corazzelli, Rosaria De Filippi, Antonio Pinto
Dendritic cells (DCs) are bone-marrow-derived immune cells accounted for a crucial role in initiating and modulating the adaptive immune response and supporting the innate immune response independently from T cells. While functioning as the most effective antigen-presenting cells within the immune system, DCs can otherwise induce tolerance in central and peripheral lymphoid organs acting therefore as suppressors rather than stimulators of the immune response. Within mechanisms regulating antitumor immunity, DCs can capture antigens from viable or damaged tumor cells and present the processed peptides to T-cells to prompt the generation and maintenance of an effective tumor-specific T-cell response...
December 2016: Critical Reviews in Oncology/hematology
https://www.readbyqxmd.com/read/27931515/autologous-adipose-derived-mesenchymal-stromal-cells-for-the-treatment-of-psoriasis-vulgaris-and-psoriatic-arthritis-a-case-report
#14
Miguel M De Jesus, Jayson S Santiago, Camille V Trinidad, Melvin E See, Kimberly R Semon, Manuel O Fernandez, Francisco S Chung
Psoriasis is a dermatologic disease of immune origins with no definitive cure. We report the Makati Medical Center experience of utilizing autologous mesenchymal stromal cells (MSCs) for one patient with psoriasis vulgaris (PV) and another with psoriatic arthritis (PA). Patients were educated and gave informed consent, according to the principles of the Declaration of Helsinki. The protocol was approved by the Cellular Transplantation Ethics Committee of the Makati Medical Center. Autologous MSCs were cultured from lipoaspirate and expanded in a clean room class 100 facility (Cellular Therapeutics Center, Makati Medical Center)...
November 2016: Cell Transplantation
https://www.readbyqxmd.com/read/27931083/the-therapeutic-potential-of-t-cell-metabolism
#15
Ali Zarrinpar, Steven J Bensinger
Transplant rejection mediated by the adaptive immune system remains a major barrier to achieving long-term tolerance and graft survival. Emerging evidence indicates that lymphocytes rapidly shift their metabolic programs in response to activation, co-stimulatory, and cytokine signals to support required effector cell differentiation and function. These observations have led to the hypothesis that manipulating the metabolic programs of immune cells could serve as a powerful therapeutic strategy for attenuating deleterious immune responses and facilitating durable tolerance in the setting of allogeneic solid organ or bone marrow transplant...
December 8, 2016: American Journal of Transplantation
https://www.readbyqxmd.com/read/27930920/indoleamine-2-3-dioxygenase-regulates-t-cell-activity-through-vav1-rac-pathway
#16
Runmei Li, Hui Li, Qian Sun, Liang Liu, Chen Zhang, Xiubao Ren
The immunoregulatory enzyme indoleamine 2,3-dioxygenase (IDO) suppresses T-cell responses and promotes immune tolerance in tumor resistance. A previous study determined that IDO inhibits Vav1 mRNA expression and the activation of Vav1 and its downstream targets in T cells in the guanine exchange factor (GEF)-independent pathway. The current study aims to determine whether IDO induces T-cell immunosuppression through Vav1/Rac signaling pathway, which is a GEF-dependent pathway. The correlation between Vav1 mRNA expressions in T cells of tumor infiltrating lymphocytes and the levels of IDO expression in lung cancer tissues from lung cancer patients was detected...
December 5, 2016: Molecular Immunology
https://www.readbyqxmd.com/read/27930307/cosmc-is-an-x-linked-inflammatory-bowel-disease-risk-gene-that-spatially-regulates-gut-microbiota-and-contributes-to-sex-specific-risk
#17
Matthew R Kudelka, Benjamin H Hinrichs, Trevor Darby, Carlos S Moreno, Hikaru Nishio, Christopher E Cutler, Jianmei Wang, Huixia Wu, Junwei Zeng, Yingchun Wang, Tongzhong Ju, Sean R Stowell, Asma Nusrat, Rheinallt M Jones, Andrew S Neish, Richard D Cummings
Inflammatory bowel disease (IBD) results from aberrant immune stimulation against a dysbiotic mucosal but relatively preserved luminal microbiota and preferentially affects males in early onset disease. However, factors contributing to sex-specific risk and the pattern of dysbiosis are largely unexplored. Core 1 β3GalT-specific molecular chaperone (Cosmc), which encodes an X-linked chaperone important for glycocalyx formation, was recently identified as an IBD risk factor by genome-wide association study. We deleted Cosmc in mouse intestinal epithelial cells (IECs) and found marked reduction of microbiota diversity in progression from the proximal to the distal gut mucosa, but not in the overlying lumen, as seen in IBD...
December 7, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27929101/hookworm-infection
#18
Alex Loukas, Peter J Hotez, David Diemert, Maria Yazdanbakhsh, James S McCarthy, Rodrigo Correa-Oliveira, John Croese, Jeffrey M Bethony
Hookworms are soil-transmitted nematode parasites that can reside for many years in the small intestine of their human hosts; Necator americanus is the predominant infecting species. Adult worms feed on the blood of a host and can cause iron deficiency anaemia, especially in high-risk populations (children and women of childbearing age). Almost 500 million people in developing tropical countries are infected, and simulation models estimate that hookworm infection is responsible for >4 million disability-adjusted life years lost annually...
December 8, 2016: Nature Reviews. Disease Primers
https://www.readbyqxmd.com/read/27928025/individualized-vaccination-of-aml-patients-in-remission-is-associated-with-induction-of-antileukemia-immunity-and-prolonged-remissions
#19
Jacalyn Rosenblatt, Richard M Stone, Lynne Uhl, Donna Neuberg, Robin Joyce, James D Levine, Jon Arnason, Malgorzata McMasters, Katarina Luptakova, Salvia Jain, Jeffrey I Zwicker, Ayad Hamdan, Vassiliki Boussiotis, David P Steensma, Daniel J DeAngelo, Ilene Galinsky, Poorvi Somaiya Dutt, Emma Logan, Mary Paty Bryant, Dina Stroopinsky, Lillian Werner, Kristen Palmer, Max Coll, Abigail Washington, Leandra Cole, Donald Kufe, David Avigan
We developed a personalized cancer vaccine in which patient-derived acute myeloid leukemia (AML) cells are fused with autologous dendritic cells, generating a hybridoma that potently stimulates broad antitumor responses. We report results obtained from the first 17 AML patients, who achieved remission after chemotherapy and were then serially vaccinated to target minimal residual disease and prevent relapse. Vaccination was well tolerated and induced inflammatory responses at the site of administration, characterized by the dense infiltration of T cells...
December 7, 2016: Science Translational Medicine
https://www.readbyqxmd.com/read/27927966/tolerogenic-dendritic-cells-from-poorly-compensated-type-1-diabetes-patients-have-decreased-ability-to-induce-stable-antigen-specific-t-cell-hyporesponsiveness-and-generation-of-suppressive-regulatory-t-cells
#20
Klára Dáňová, Anna Grohová, Pavla Strnadová, David P Funda, Zdeněk Šumník, Jan Lebl, Ondřej Cinek, Štěpánka Průhová, Stanislava Koloušková, Barbora Obermannová, Lenka Petruželková, Anna Šedivá, Petra Fundová, Karsten Buschard, Radek Špíšek, Lenka Palová-Jelínková
Tolerogenic dendritic cells (tolDCs) may offer an interesting intervention strategy to re-establish Ag-specific tolerance in autoimmune diseases, including type 1 diabetes (T1D). T1D results from selective destruction of insulin-producing β cells leading to hyperglycemia that, in turn, specifically affects a patient's immune system. In this study, we prepared monocyte-derived tolDCs modulated by dexamethasone and vitamin D2 from 31 T1D patients with optimal glycemic control and 60 T1D patients with suboptimal glycemic control and assessed their tolerogenic properties in correlation with metabolic state of patients...
December 7, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
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