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T cell regulation

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https://www.readbyqxmd.com/read/28346517/cd22-is-required-for-formation-of-memory-b-cell-precursors-within-germinal-centers
#1
Craig P Chappell, Kevin E Draves, Edward A Clark
CD22 is a BCR co-receptor that regulates B cell signaling, proliferation and survival and is required for T cell-independent Ab responses. To investigate the role of CD22 during T cell-dependent (TD) Ab responses and memory B cell formation, we analyzed Ag-specific B cell responses generated by wild-type (WT) or CD22-/- B cells following immunization with a TD Ag. CD22-/- B cells mounted normal early Ab responses yet failed to generate either memory B cells or long-lived plasma cells, whereas WT B cells formed both populations...
2017: PloS One
https://www.readbyqxmd.com/read/28346506/specific-expression-of-novel-long-non-coding-rnas-in-high-hyperdiploid-childhood-acute-lymphoblastic-leukemia
#2
Mathieu Lajoie, Simon Drouin, Maxime Caron, Pascal St-Onge, Manon Ouimet, Romain Gioia, Marie-Hélène Lafond, Ramon Vidal, Chantal Richer, Karim Oualkacha, Arnaud Droit, Daniel Sinnett
Pre-B cell childhood acute lymphoblastic leukemia (pre-B cALL) is a heterogeneous disease involving many subtypes typically stratified using a combination of cytogenetic and molecular-based assays. These methods, although widely used, rely on the presence of known chromosomal translocations, which is a limiting factor. There is therefore a need for robust, sensitive, and specific molecular biomarkers unaffected by such limitations that would allow better risk stratification and consequently better clinical outcome...
2017: PloS One
https://www.readbyqxmd.com/read/28346402/large-scale-design-of-robust-genetic-circuits-with-multiple-inputs-and-outputs-for-mammalian-cells
#3
Benjamin H Weinberg, N T Hang Pham, Leidy D Caraballo, Thomas Lozanoski, Adrien Engel, Swapnil Bhatia, Wilson W Wong
Engineered genetic circuits for mammalian cells often require extensive fine-tuning to perform as intended. We present a robust, general, scalable system, called 'Boolean logic and arithmetic through DNA excision' (BLADE), to engineer genetic circuits with multiple inputs and outputs in mammalian cells with minimal optimization. The reliability of BLADE arises from its reliance on recombinases under the control of a single promoter, which integrates circuit signals on a single transcriptional layer. We used BLADE to build 113 circuits in human embryonic kidney and Jurkat T cells and devised a quantitative, vector-proximity metric to evaluate their performance...
March 27, 2017: Nature Biotechnology
https://www.readbyqxmd.com/read/28346226/a-tlr9-dependent-checkpoint-governs-b-cell-responses-to-dna-containing-antigens
#4
Vishal J Sindhava, Michael A Oropallo, Krishna Moody, Martin Naradikian, Lauren E Higdon, Lin Zhou, Arpita Myles, Nathaniel Green, Kerstin Nündel, William Stohl, Amanda M Schmidt, Wei Cao, Stephanie Dorta-Estremera, Taku Kambayashi, Ann Marshak-Rothstein, Michael P Cancro
Mature B cell pools retain a substantial proportion of polyreactive and self-reactive clonotypes, suggesting that activation checkpoints exist to reduce the initiation of autoreactive B cell responses. Here, we have described a relationship among the B cell receptor (BCR), TLR9, and cytokine signals that regulate B cell responses to DNA-containing antigens. In both mouse and human B cells, BCR ligands that deliver a TLR9 agonist induce an initial proliferative burst that is followed by apoptotic death. The latter mechanism involves p38-dependent G1 cell-cycle arrest and subsequent intrinsic mitochondrial apoptosis and is shared by all preimmune murine B cell subsets and CD27- human B cells...
March 27, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28345617/stimulation-of-adult-hippocampal-neurogenesis-by-physical-exercise-and-enriched-environment-is-disturbed-in-a-cadasil-mouse-model
#5
C Klein, S Schreyer, F E Kohrs, P Elhamoury, A Pfeffer, T Munder, B Steiner
In the course of CADASIL (Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy), a dysregulated adult hippocampal neurogenesis has been suggested as a potential mechanism for early cognitive decline. Previous work has shown that mice overexpressing wild type Notch3 and mice overexpressing Notch3 with a CADASIL mutation display impaired cell proliferation and survival of newly born hippocampal neurons prior to vascular abnormalities. Here, we aimed to elucidate how the long-term survival of these newly generated neurons is regulated by Notch3...
March 27, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28344884/the-differentiation-and-plasticity-of-tc17-cells-are-regulated-by-ctla-4-mediated-effects-on-stats
#6
Aditya Arra, Holger Lingel, Benno Kuropka, Jonas Pick, Tina Schnoeder, Thomas Fischer, Christian Freund, Mandy Pierau, Monika C Brunner-Weinzierl
As the blockade of inhibitory surface-molecules such as CTLA-4 on T cells has led to recent advances in antitumor immune therapy, there is great interest in identifying novel mechanisms of action of CD8(+) T cells to evoke effective cytotoxic antitumor responses. Using in vitro and in vivo models, we investigated the molecular pathways underlying the CTLA-4-mediated differentiation of IL-17-producing CD8(+) T cells (Tc17 cells) that strongly impairs cytotoxicity. Our studies demonstrate that Tc17 cells lacking CTLA-4 signaling have limited production of STAT3-target gene products such as IL-17, IL-21, IL-23R and RORγt...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28344859/hla-class-ii-antigen-processing-pathway-in-tumors-molecular-defects-and-clinical-relevance
#7
REVIEW
Barbara Seliger, Matthias Kloor, Soldano Ferrone
The human leukocyte antigen (HLA) class II antigen-processing machinery (APM) presents to cognate CD4(+) T-cells antigenic peptides mainly generated from exogeneous proteins in the endocytic compartment. These CD4(+) T cells exert helper function, but may also act as effector cells, thereby recognizing HLA class II antigen-expressing tumor cells. Thus, HLA class II antigen expression by tumor cells influences the tumor antigen (TA)-specific immune responses and, depending on the cancer type, the clinical course of the disease...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28344807/ipilimumab-induced-thrombotic-thrombocytopenic-purpura-ttp
#8
Jeanelle King, Javier de la Cruz, Jose Lutzky
BACKGROUND: CTLA-4 (Cytotoxic T-lymphocyte-associated protein 4) was the first immune checkpoint receptor clinically targeted for use in cancer treatment. It is expressed exclusively on T-cells where its primary role is to regulate the amplitude of the early stages of T-cell activation.1 Ipilimumab, a CTLA-4 blocking antibody, has been widely used for the treatment of patients with high risk and metastatic melanoma. Given its mechanism of action and consequent immune activation, the side effect profile of this drug greatly differs from that of standard cytotoxic chemotherapy...
2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28344516/ulinastatin-ameliorates-tissue-damage-of-severe-acute-pancreatitis-through-modulating-regulatory-t-cells
#9
Yu Pan, Haizong Fang, Fengchun Lu, Minggui Pan, Fei Chen, Ping Xiong, Yi Yao, Heguang Huang
BACKGROUND: Ulinastatin or urinary trypsin inhibitor (UTI) has been shown to ameliorate the inflammatory response induced by experimental severe acute pancreatitis (SAP) and hence reduce the mortality, however the mechanism of its action remains incompletely understood. We have investigated the effect of ulinastatin on regulatory T-cells (Tregs) in an established rat model of SAP. METHODS: We established a rat SAP model by injecting 5% Na-taurocholate into the pancreatic duct and treated the SAP rats with ulinastatin with different dose level (5000, 10000, 30000 U/kg) through intraperitoneal injection at 0, 6 and 12 h...
2017: Journal of Inflammation
https://www.readbyqxmd.com/read/28344320/dpp4-truncated-gm-csf-il-3-manifest-distinct-receptor-binding-regulatory-functions-compared-to-their-full-length-forms
#10
H A O'Leary, M Capitano, S Cooper, C Mantel, H S Boswell, R Kapur, B Ramdas, R Chan, L Deng, C-K Qu, H E Broxmeyer
Dipeptidylpeptidase 4 (DPP4/CD26) enzymatically cleaves select penultimate amino acids of proteins, including colony stimulating factors (CSFs), and has been implicated in cellular regulation. To better understand the role of DPP4 regulation of hematopoiesis, we analyzed the activity of DPP4 on the surface of immature blood cells and then comparatively assessed the interactions and functional effects of full-length (FL) and DPP4 truncated factors [(T)-GM-CSF and- IL-3] on both in vitro and in vivo models of normal and leukemic cells...
March 27, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28344319/pd-l1-is-commonly-expressed-and-transcriptionally-regulated-by-stat3-and-myc-in-alk-negative-anaplastic-large-cell-lymphoma
#11
V Atsaves, N Tsesmetzis, D Chioureas, L Kis, V Leventaki, E Drakos, T Panaretakis, D Grander, L J Medeiros, K H Young, G Z Rassidakis
Leukemia accepted article preview online, 27 March 2017. doi:10.1038/leu.2017.103.
March 27, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28344171/lipopolysaccharide-induced-interleukin-6-production-is-mediated-through-activation-of-erk-1-2-p38-mapk-mek-and-nf%C3%AE%C2%BAb-in-chicken-thrombocytes
#12
C Winkler, F Ferdous, M Dimmick, T Scott
Thrombocytes express Toll-like receptor 4 and apparently use both mitogen-activated protein kinase (MAPK) and nuclear factor kappa-light-chain-enhancer of activated B cells (NFKB) pathways for nuclear signaling. However, it is not well known if the same enzyme systems found in mammalian cells are fully functional in chickens. Therefore, kinase inhibitors were used with thrombocytes to block kinases in lipopolysaccharide (LPS) stimulated cells to determine if interleukin (IL)-6 expression and production would be diminished...
March 23, 2017: Developmental and Comparative Immunology
https://www.readbyqxmd.com/read/28344153/plant-hormone-cytokinins-control-cell-cycle-progression-and-plastid-replication-in-apicomplexan-parasites
#13
Syed Bilal Ahmad Andrabi, Michiru Tahara, Ryuma Matsubara, Tomoko Toyama, Hiroka Aonuma, Hitoshi Sakakibara, Makoto Suematsu, Kazuyuki Tanabe, Tomoyoshi Nozaki, Kisaburo Nagamune
Cytokinins are plant hormones that are involved in regulation of cell proliferation, cell cycle progression, and cell and plastid development. Here, we show that the apicomplexan parasites Toxoplasma gondii and Plasmodium berghei, an opportunistic human pathogen and a rodent malaria agent, respectively, produce cytokinins via a biosynthetic pathway similar to that in plants. Cytokinins regulate the growth and cell cycle progression of T. gondii by mediating expression of the cyclin gene TgCYC4. A natural form of cytokinin, trans-zeatin (t-zeatin), upregulated expression of this cyclin, while a synthetic cytokinin, thidiazuron, downregulated its expression...
March 23, 2017: Parasitology International
https://www.readbyqxmd.com/read/28344041/stat5-signaling-in-kisspeptin-cells-regulates-the-timing-of-puberty
#14
Marina Augusto Silveira, Isadora C Furigo, Thais T Zampieri, Tabata M Bohlen, Daniella G de Paula, Celso Rodrigues Franci, Jose Donato, Renata Frazao
Previous studies have shown that kisspeptin neurons are important mediators of prolactin's effects on reproduction. However, the cellular mechanisms recruited by prolactin to affect kisspeptin neurons remain unknown. Using whole-cell patch-clamp recordings of brain slices from kisspeptin reporter mice, we observed that 20% of kisspeptin neurons in the anteroventral periventricular nucleus was indirectly depolarized by prolactin via an unknown population of prolactin responsive neurons. This effect required the phosphatidylinositol 3-kinase signaling pathway...
March 23, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28343758/synergistic-expression-of-histone-deacetylase-9-and-matrix-metalloproteinase-12-in-m4-macrophages-in-advanced-carotid-plaques
#15
N K J Oksala, I Seppälä, R Rahikainen, K-M Mäkelä, E Raitoharju, T Illig, N Klopp, I Kholova, R Laaksonen, P J Karhunen, V P Hytönen, T Lehtimäki
OBJECTIVE/BACKGROUND: Expression patterns and association with cell specific gene expression signatures of the epigenetic regulator histone deacetylase 9 (HDAC9) and matrix metalloproteinase 12 (MMP12) in human plaque are not known. METHODS: This was a prospective cohort study. Genome wide expression analysis was performed in carotid, femoral, aortic plaques (n = 68) and left internal thoracic (LITA) controls (n = 28) and plaque histological severity assessed...
March 23, 2017: European Journal of Vascular and Endovascular Surgery
https://www.readbyqxmd.com/read/28343630/de-novo-truncating-mutations-in-the-last-and-penultimate-exons-of-ppm1d-cause-an-intellectual-disability-syndrome
#16
Sandra Jansen, Sinje Geuer, Rolph Pfundt, Rachel Brough, Priyanka Ghongane, Johanna C Herkert, Elysa J Marco, Marjolein H Willemsen, Tjitske Kleefstra, Mark Hannibal, Joseph T Shieh, Sally Ann Lynch, Frances Flinter, David R FitzPatrick, Alice Gardham, Birgitta Bernhard, Nicola Ragge, Ruth Newbury-Ecob, Raphael Bernier, Malin Kvarnung, E A Helena Magnusson, Marja W Wessels, Marjon A van Slegtenhorst, Kristin G Monaghan, Petra de Vries, Joris A Veltman, Christopher J Lord, Lisenka E L M Vissers, Bert B A de Vries
Intellectual disability (ID) is a highly heterogeneous disorder involving at least 600 genes, yet a genetic diagnosis remains elusive in ∼35%-40% of individuals with moderate to severe ID. Recent meta-analyses statistically analyzing de novo mutations in >7,000 individuals with neurodevelopmental disorders highlighted mutations in PPM1D as a possible cause of ID. PPM1D is a type 2C phosphatase that functions as a negative regulator of cellular stress-response pathways by mediating a feedback loop of p38-p53 signaling, thereby contributing to growth inhibition and suppression of stress-induced apoptosis...
March 18, 2017: American Journal of Human Genetics
https://www.readbyqxmd.com/read/28342869/microrna-448-promotes-multiple-sclerosis-development-through-induction-of-th17-response-through-targeting-protein-tyrosine-phosphatase-non-receptor-type-2-ptpn2
#17
Rihan Wu, Qinyu He, Haitao Chen, Miao Xu, Ning Zhao, Ying Xiao, Qian-Qian Tu, Wenjun Zhang, Xiaoying Bi
Multiple sclerosis (MS) is an immune-mediated demyelinating disease of the central nervous system, and its pathogenesis remains largely unclear. Much attention has been paid to the role of microRNAs (miRs) in regulation of autoimmune disease. Here, we found, for the first time, that miR-448 expression was significantly increased in periphery blood mononuclear cells (PBMC) and cerebrospinal fluid (CSF) of patients with MS, and its expression positively correlated with the disease severity. We further demonstrated that CD4(+) T cells, especially the Th17 lineage, were the major source of miR-448 expression...
March 22, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28342814/tear-cytokine-profile-of-glaucoma-patients-treated-with-preservative-free-or-preserved-latanoprost
#18
Jose M Martinez-de-la-Casa, Francisco Perez-Bartolome, Elena Urcelay, Jose L Santiago, Javier Moreno-Montañes, Pedro Arriola-Villalobos, Jose M Benitez-Del-Castillo, Julian Garcia-Feijoo
PURPOSE: To determine variations in cytokine levels of glaucoma patients treated either with preservative-free latanoprost or preserved latanoprost, relative to healthy individuals. METHODS: Tear samples were collected from 39 healthy subjects, 20 glaucoma patients treated with preserved latanoprost, and 20 patients treated with preservative-free latanoprost. A set of 27 inflammatory cytokines was analyzed in each group, including interleukin (IL)-1β, IL-1ra, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL9, IL-10, IL-12 (p70), IL-13, IL-15, IL-17, eotaxin, fibroblast growth factor (FGF) basic, granulocyte colony stimulating factor (G-CSF), granulocyte monocyte colony stimulating factor (GM-CSF), interferon (IFN)-γ, interferon gamma-induced protein (IP)-10, monocyte chemo attractant protein (MCP)-1MCAF, macrophage inflammatory protein (MIP)-1α, MIP-1β, platelet-derived growth factor (PDGF)-BB, regulated on activation, normal T cell expressed and secreted (RANTES), tumor necrosis factor (TNF)-α and vascular endothelial growth factor (VEGF)...
March 22, 2017: Ocular Surface
https://www.readbyqxmd.com/read/28342734/integration-of-microbiome-and-epigenome-to-decipher-the-pathogenesis-of-autoimmune-diseases
#19
REVIEW
Beidi Chen, Luxi Sun, Xuan Zhang
The interaction between genetic predisposition and environmental factors are of great significance in the pathogenesis and development of autoimmune diseases (AIDs). The human mucosa is the most frequent site that interacts with the exterior environment, and commensal microbiota at the gut and other human mucosal cavities play a crucial role in the regulation of immune system. Growing evidence has shown that the compositional and functional changes of mucosal microbiota are closely related to AIDs. Gut dysbiosis not only influence the expression level of Toll-like receptors (TLRs) of antigen presenting cells, but also contribute to Th17/Treg imbalance...
March 22, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28341702/nras-destines-tumor-cells-to-the-lungs
#20
Anastasios D Giannou, Antonia Marazioti, Nikolaos I Kanellakis, Ioanna Giopanou, Ioannis Lilis, Dimitra E Zazara, Giannoula Ntaliarda, Danai Kati, Vasileios Armenis, Georgia A Giotopoulou, Anthi C Krontira, Marina Lianou, Theodora Agalioti, Malamati Vreka, Maria Papageorgopoulou, Sotirios Fouzas, Dimitrios Kardamakis, Ioannis Psallidas, Magda Spella, Georgios T Stathopoulos
The lungs are frequently affected by cancer metastasis. Although NRAS mutations have been associated with metastatic potential, their exact role in lung homing is incompletely understood. We cross-examined the genotype of various tumor cells with their ability for automatic pulmonary dissemination, modulated NRAS expression using RNA interference and NRAS overexpression, identified NRAS signaling partners by microarray, and validated them using Cxcr1- and Cxcr2-deficient mice. Mouse models of spontaneous lung metastasis revealed that mutant or overexpressed NRAS promotes lung colonization by regulating interleukin-8-related chemokine expression, thereby initiating interactions between tumor cells, the pulmonary vasculature, and myeloid cells...
March 24, 2017: EMBO Molecular Medicine
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