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https://www.readbyqxmd.com/read/28339682/the-effects-of-interleukin-2-on-immune-response-regulation
#1
Ryan S Waters, Justin S A Perry, SunPil Han, Bibiana Bielekova, Tomas Gedeon
The immune system has many adaptive and dynamic components that are regulated to ensure appropriate, precise and rapid response to a foreign pathogen. A delayed or inadequate immune response can lead to prolonged disease, while an excessive or under-regulated response can lead to autoimmunity. The cytokine, interleukin-2 (IL-2) and its receptor IL-2R play an important role in maintaining this balance.The IL-2 receptor transduces pSTAT5 signal through both the intermediate and high affinity receptors, which differ from each other by the presence of CD25 chain in IL-2 receptor...
February 20, 2017: Mathematical Medicine and Biology: a Journal of the IMA
https://www.readbyqxmd.com/read/28337196/salmonella-typhi-porins-ompc-and-ompf-are-potent-adjuvants-for-t-dependent-and-t-independent-antigens
#2
Marisol Pérez-Toledo, Nuriban Valero-Pacheco, Rodolfo Pastelin-Palacios, Cristina Gil-Cruz, Christian Perez-Shibayama, Mario A Moreno-Eutimio, Ingeborg Becker, Sonia Mayra Pérez-Tapia, Lourdes Arriaga-Pizano, Adam F Cunningham, Armando Isibasi, Laura C Bonifaz, Constantino López-Macías
Several microbial components, such as bacterial DNA and flagellin, have been used as experimental vaccine adjuvants because of their inherent capacity to efficiently activate innate immune responses. Likewise, our previous work has shown that the major Salmonella Typhi (S. Typhi) outer membrane proteins OmpC and OmpF (porins) are highly immunogenic protective antigens that efficiently stimulate innate and adaptive immune responses in the absence of exogenous adjuvants. Moreover, S. Typhi porins induce the expression of costimulatory molecules on antigen-presenting cells through toll-like receptor canonical signaling pathways...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28331856/the-immunogenicity-of-hla-class-ii-mismatches-the-predicted-presentation-of-nonself-allo-hla-derived-peptide-by-the-hla-dr-phenotype-of-the-recipient-is-associated-with-the-formation-of-dsa
#3
Vadim Jucaud
The identification of permissible HLA class II mismatches can prevent DSA in mismatched transplantation. The HLA-DR phenotype of recipients contributes to DSA formation by presenting allo-HLA-derived peptides to T-helper cells, which induces the differentiation of B cells into plasma cells. Comparing the binding affinity of self and nonself allo-HLA-derived peptides for recipients' HLA class II antigens may distinguish immunogenic HLA mismatches from nonimmunogenic ones. The binding affinities of allo-HLA-derived peptides to recipients' HLA-DR and HLA-DQ antigens were predicted using the NetMHCIIpan 3...
2017: Journal of Immunology Research
https://www.readbyqxmd.com/read/28326562/liposome-encapsulated-hemoglobin-accelerates-skin-wound-healing-in-diabetic-db-db-mice
#4
Tsuyoshi Fukui, Akira T Kawaguchi, Susumu Takekoshi, Muneo Miyasaka, Hideaki Sumiyoshi, Rica Tanaka
Since liposome-encapsulated hemoglobin with high O2 affinity (h-LEH, P50 O2  = 10 mm Hg) has been reported to accelerate skin wound healing in normal mice, it was tested in dB/dB mice with retarded wound healing, as seen in human diabetics. Two full-thickness dorsal wounds 6 mm in diameter encompassed by silicone stents were created in dB/dB mice. Two days later (day 2), the animals were randomly assigned to receive intravenous h-LEH (2 mL/kg, n = 7) or saline (2 mL/kg, n = 7). The same treatment was repeated 4 days after wounding (day 4), and the size of the skin lesions was analyzed by photography, surface perfusion was detected by Laser-Doppler imager, and plasma cytokines and chemokines were determined on days 0, 2, 4, and 7, when all animals were euthanized for morphological studies...
March 21, 2017: Artificial Organs
https://www.readbyqxmd.com/read/28325833/the-unique-prodomain-of-t-cadherin-plays-a-key-role-in-adiponectin-binding-with-the-essential-extracellular-cadherin-repeats-1-and-2
#5
Shiro Fukuda, Shunbun Kita, Yoshinari Obata, Yuya Fujishima, Hirofumi Nagao, Shigeki Masuda, Yoshimitsu Tanaka, Hitoshi Nishizawa, Tohru Funahashi, Junichi Takagi, Norikazu Maeda, Iichiro Shimomura
Adiponectin, an adipocyte-derived circulating protein, accumulates in the heart, vascular endothelium, and skeletal muscles through an interaction with T-cadherin (T-cad), a unique glycosylphosphatidylinositol (GPI)-anchored cadherin. Recent studies have suggested that this interaction is essential for adiponectin-mediated cardiovascular protection. However, the precise protein-protein interaction between adiponectin and T-cad remains poorly characterized. Using ELISA-based and surface plasmon analyses, we report here that T-cad fused with IgG Fc as a fusion-tag by replacing its GPI-anchor specifically bound both hexameric and larger multimeric adiponectin with a dissociation constant of approximately 1...
March 21, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28322160/an-efficient-transient-expression-system-for-enhancing-generation-of-monoclonal-antibodies-in-293-suspension-cells
#6
Guoquan Zhang, Jie Liu, Wanting Fan, Qianyi Chen, Bin Shi
BACKGROUND: Recombinant monoclonal antibodies (mAbs) are useful in research, diagnosis, and therapy. The increased demands of recombinant mAbs require efficient production systems. A variety of expression vectors have been developed for stable or transient production of mAb in mammalian cells. However, though a few commercial expression systems of mAbs can be listened, the high expense often impedes academia researches. METHODS: In this study, we described the development of a transient mammalian system based on a bicistronic vector, which contains internal ribosome entry site (IRES) and enhancer elements to express IgG1 light chain (LC) and heavy chain (HC) in one transcript...
March 20, 2017: Current Pharmaceutical Biotechnology
https://www.readbyqxmd.com/read/28320776/epigenomic-promoter-alterations-amplify-gene-isoform-and-immunogenic-diversity-in-gastric-adenocarcinoma
#7
Aditi Qamra, Manjie Xing, Nisha Padmanabhan, Jeffrey Jun Ting Kwok, Shenli Zhang, Xu Chang, Yan Shan Leong, Ai Ping Lee Lim, Qianqao Tang, WenFong Ooi, Joyce Suling Lin, Tannistha Nandi, Xiaosai Yao, Xuewen Ong, Minghui Lee, Su Ting Tay, Angie Tan Lay Keng, Erna Gondo Santoso, Cedric Chuan Young Ng, Alvin Ng, Apinya Jusakul, Duane Smoot, Hassan Ashktorab, Sun Young Rha, Khay Guan Yeoh, Wei Peng Yong, Pierce K H Chow, Weng Hoong Chan, Hock Soo Ong, Khee Chee Soo, Kyoung-Mee Kim, Wai Keong Wong, Steven G Rozen, Bin Tean Teh, Dennis Kappei, Jeeyun Lee, John Connolly, Patrick Tan
Promoter elements play important roles in isoform and cell-type specific expression. We surveyed the epigenomic promoter landscape of gastric adenocarcinoma (GC), analyzing 110 chromatin profiles (H3K4me3, H3K4me1, H3K27ac) of primary GCs, GC lines, and non-malignant gastric tissues. We identified ~2000 promoter alterations (somatic promoters), many deregulated in various epithelial malignancies and mapping frequently to alternative promoters within the same gene, generating potential pro-oncogenic isoforms (RASA3)...
March 20, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28320297/selection-of-progesterone-derivatives-specific-to-membrane-progesterone-receptors
#8
A V Polikarpova, A A Maslakova, I S Levina, L E Kulikova, Y V Kuznetsov, A A Guseva, T A Shchelkunova, I V Zavarzin, O V Smirnova
The search of selective agonists and antagonists of membrane progesterone receptors (mPRs) is a starting point for the study of progesterone signal transduction mechanisms mediated by mPRs, distinct from nuclear receptors. According to preliminary data, the ligand affinity for mPRs differs significantly from that for classical nuclear progesterone receptors (nPRs), which might indicate structural differences in the ligand-binding pocket of these proteins. In the present work, we analyzed the affinity of several progesterone derivatives for mPRs of human pancreatic adenocarcinoma BxPC3 cell line that is characterized by a high level of mPR mRNA expression and by the absence of expression of nPR mRNA...
February 2017: Biochemistry. Biokhimii︠a︡
https://www.readbyqxmd.com/read/28319730/deconstructing-the-germinal-center-one-cell-at-a-time
#9
REVIEW
Chad R Dufaud, Louise J McHeyzer-Williams, Michael G McHeyzer-Williams
Successful vaccination relies on driving the immune response towards high specificity, affinity and longevity. Germinal centers facilitate the evolution of antigen-specific B cells by iterative rounds of diversification, selection, and differentiation to memory and plasma cells. Experimental evidence points to B cell receptor affinity and amount of antigen presented to follicular helper T cells as main drivers of clonal evolution. Concurrent studies suggest that modifiers of cognate contact, temporal mechanisms, and stochastic factors can also shape diversity and influence differentiation to memory and plasma cells, but molecular pathways driving these selection decisions are unresolved...
March 17, 2017: Current Opinion in Immunology
https://www.readbyqxmd.com/read/28316767/type-ii-enteropathy-associated-t-cell-lymphoma-a-rare-report-from-iran
#10
Neda Nozari
Type II enteropathy-associated T-cell lymphoma (EATL) is a rare disease that is reported from Asia, especially from Taiwan. In this paper, we present a patient from Iran (Arab) with Type II EATL whose disease was not associated with celiac disease or Epstein-Barr virus (EBV) infection. The patient died due to intestinal perforation during the first chemotherapy. Type II EATL is a gastrointestinal lymphoma with poor prognosis and a high affinity for intestinal perforation. Early detection of EATL II is essential for chemotherapy prior to the onset of malnutrition symptoms...
January 2017: Middle East Journal of Digestive Diseases
https://www.readbyqxmd.com/read/28303891/il-21-restricts-t-follicular-regulatory-t-cell-proliferation-through-bcl-6-mediated-inhibition-of-responsiveness-to-il-2
#11
Christoph Jandl, Sue M Liu, Pablo F Cañete, Joanna Warren, William E Hughes, Alexis Vogelzang, Kylie Webster, Maria E Craig, Gulbu Uzel, Alexander Dent, Polina Stepensky, Bärbel Keller, Klaus Warnatz, Jonathan Sprent, Cecile King
T follicular regulatory (Tfr) cells control the magnitude and specificity of the germinal centre reaction, but how regulation is contained to ensure generation of high-affinity antibody is unknown. Here we show that this balance is maintained by the reciprocal influence of interleukin (IL)-2 and IL-21. The number of IL-2-dependent FoxP3(+) regulatory T cells is increased in the peripheral blood of human patients with loss-of-function mutations in the IL-21 receptor (IL-21R). In mice, IL-21:IL-21R interactions influence the phenotype of T follicular cells, reducing the expression of CXCR4 and inhibiting the expansion of Tfr cells after T-cell-dependent immunization...
March 17, 2017: Nature Communications
https://www.readbyqxmd.com/read/28303660/brazilin-inhibits-prostatic-acidic-phosphatase-fibrillogenesis-and-reduces-its-cytotoxicity
#12
Ming Li, Xiaoyan Dong, Yang Liu, Yan Sun
The 39-amino acid peptide fragment derived from prostatic acidic phosphatase (PAP), PAP248-286, is secreted in large amount into human semen and form amyloid fibrils. The fibrils can capture HIV virions and increase the attachment of virions to target cells, so they are called semen-derived enhancer of virus infection (SEVI). Therefore, it is of significance to inhibit the formation of PAP248-286 amyloid fibrils. Herein, we have demonstrated that brazilin could effectively inhibit PAP248-286 aggregation. The inhibition effect increased with increasing brazilin concentration...
March 16, 2017: Chemistry, An Asian Journal
https://www.readbyqxmd.com/read/28302091/development-of-a-test-that-measures-real-time-her2-signaling-function-in-live-breast-cancer-cell-lines-and-primary-cells
#13
Yao Huang, David J Burns, Benjamin E Rich, Ian A MacNeil, Abhijit Dandapat, Sajjad M Soltani, Samantha Myhre, Brian F Sullivan, Carol A Lange, Leo T Furcht, Lance G Laing
BACKGROUND: Approximately 18-20% of all human breast cancers have overexpressed human epidermal growth factor receptor 2 (HER2). Standard clinical practice is to treat only overexpressed HER2 (HER2+) cancers with targeted anti-HER2 therapies. However, recent analyses of clinical trial data have found evidence that HER2-targeted therapies may benefit a sub-group of breast cancer patients with non-overexpressed HER2. This suggests that measurement of other biological factors associated with HER2 cancer, such as HER2 signaling pathway activity, should be considered as an alternative means of identifying patients eligible for HER2 therapies...
March 16, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28298421/mimicry-of-an-hiv-broadly-neutralizing-antibody-epitope-with-a-synthetic-glycopeptide
#14
S Munir Alam, Baptiste Aussedat, Yusuf Vohra, R Ryan Meyerhoff, Evan M Cale, William E Walkowicz, Nathan A Radakovich, Kara Anasti, Lawrence Armand, Robert Parks, Laura Sutherland, Richard Scearce, M Gordon Joyce, Marie Pancera, Aliaksandr Druz, Ivelin S Georgiev, Tarra Von Holle, Amanda Eaton, Christopher Fox, Steven G Reed, Mark Louder, Robert T Bailer, Lynn Morris, Salim S Abdool-Karim, Myron Cohen, Hua-Xin Liao, David C Montefiori, Peter K Park, Alberto Fernández-Tejada, Kevin Wiehe, Sampa Santra, Thomas B Kepler, Kevin O Saunders, Joseph Sodroski, Peter D Kwong, John R Mascola, Mattia Bonsignori, M Anthony Moody, Samuel Danishefsky, Barton F Haynes
A goal for an HIV-1 vaccine is to overcome virus variability by inducing broadly neutralizing antibodies (bnAbs). One key target of bnAbs is the glycan-polypeptide at the base of the envelope (Env) third variable loop (V3). We have designed and synthesized a homogeneous minimal immunogen with high-mannose glycans reflective of a native Env V3-glycan bnAb epitope (Man9-V3). V3-glycan bnAbs bound to Man9-V3 glycopeptide and native-like gp140 trimers with similar affinities. Fluorophore-labeled Man9-V3 glycopeptides bound to bnAb memory B cells and were able to be used to isolate a V3-glycan bnAb from an HIV-1-infected individual...
March 15, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28298420/staged-induction-of-hiv-1-glycan-dependent-broadly-neutralizing-antibodies
#15
Mattia Bonsignori, Edward F Kreider, Daniela Fera, R Ryan Meyerhoff, Todd Bradley, Kevin Wiehe, S Munir Alam, Baptiste Aussedat, William E Walkowicz, Kwan-Ki Hwang, Kevin O Saunders, Ruijun Zhang, Morgan A Gladden, Anthony Monroe, Amit Kumar, Shi-Mao Xia, Melissa Cooper, Mark K Louder, Krisha McKee, Robert T Bailer, Brendan W Pier, Claudia A Jette, Garnett Kelsoe, Wilton B Williams, Lynn Morris, John Kappes, Kshitij Wagh, Gift Kamanga, Myron S Cohen, Peter T Hraber, David C Montefiori, Ashley Trama, Hua-Xin Liao, Thomas B Kepler, M Anthony Moody, Feng Gao, Samuel J Danishefsky, John R Mascola, George M Shaw, Beatrice H Hahn, Stephen C Harrison, Bette T Korber, Barton F Haynes
A preventive HIV-1 vaccine should induce HIV-1-specific broadly neutralizing antibodies (bnAbs). However, bnAbs generally require high levels of somatic hypermutation (SHM) to acquire breadth, and current vaccine strategies have not been successful in inducing bnAbs. Because bnAbs directed against a glycosylated site adjacent to the third variable loop (V3) of the HIV-1 envelope protein require limited SHM, the V3-glycan epitope is an attractive vaccine target. By studying the cooperation among multiple V3-glycan B cell lineages and their coevolution with autologous virus throughout 5 years of infection, we identify key events in the ontogeny of a V3-glycan bnAb...
March 15, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28297712/cd32a-is-a-marker-of-a-cd4-t-cell-hiv-reservoir-harbouring-replication-competent-proviruses
#16
Benjamin Descours, Gaël Petitjean, José-Luis López-Zaragoza, Timothée Bruel, Raoul Raffel, Christina Psomas, Jacques Reynes, Christine Lacabaratz, Yves Levy, Olivier Schwartz, Jean Daniel Lelievre, Monsef Benkirane
The persistence of the HIV reservoir in infected individuals is a major obstacle to the development of a cure for HIV. Here, using an in vitro model of HIV-infected quiescent CD4 T cells, we reveal a gene expression signature of 103 upregulated genes that are specific for latently infected cells, including genes for 16 transmembrane proteins. In vitro screening for surface expression in HIV-infected quiescent CD4 T cells shows that the low-affinity receptor for the immunoglobulin G Fc fragment, CD32a, is the most highly induced, with no detectable expression in bystander cells...
March 15, 2017: Nature
https://www.readbyqxmd.com/read/28297661/t-follicular-helper-cells-promote-a-beneficial-gut-ecosystem-for-host-metabolic-homeostasis-by-sensing-microbiota-derived-extracellular-atp
#17
Lisa Perruzza, Giorgio Gargari, Michele Proietti, Bruno Fosso, Anna Maria D'Erchia, Caterina Elisa Faliti, Tanja Rezzonico-Jost, Daniela Scribano, Laura Mauri, Diego Colombo, Giovanni Pellegrini, Annalisa Moregola, Catherine Mooser, Graziano Pesole, Mauro Nicoletti, Giuseppe Danilo Norata, Markus B Geuking, Kathy D McCoy, Simone Guglielmetti, Fabio Grassi
The ATP-gated ionotropic P2X7 receptor regulates T follicular helper (Tfh) cell abundance in the Peyer's patches (PPs) of the small intestine; deletion of P2rx7, encoding for P2X7, in Tfh cells results in enhanced IgA secretion and binding to commensal bacteria. Here, we show that Tfh cell activity is important for generating a diverse bacterial community in the gut and that sensing of microbiota-derived extracellular ATP via P2X7 promotes the generation of a proficient gut ecosystem for metabolic homeostasis...
March 14, 2017: Cell Reports
https://www.readbyqxmd.com/read/28293238/role-of-memory-t-cells-in-allograft-rejection-and-tolerance
#18
REVIEW
Gilles Benichou, Bruno Gonzalez, Jose Marino, Katayoun Ayasoufi, Anna Valujskikh
Memory T cells are characterized by their low activation threshold, robust effector functions, and resistance to conventional immunosuppression and costimulation blockade. Unlike their naïve counterparts, memory T cells reside in and recirculate through peripheral non-lymphoid tissues. Alloreactive memory T cells are subdivided into different categories based on their origins, phenotypes, and functions. Recipients whose immune systems have been directly exposed to allogeneic major histocompatibility complex (MHC) molecules display high affinity alloreactive memory T cells...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28293236/interferon-lambda-modulating-immunity-in-infectious-diseases
#19
REVIEW
Mohammedyaseen Syedbasha, Adrian Egli
Interferon lambdas (IFN-λs; IFNL1-4) modulate immunity in the context of infections and autoimmune diseases, through a network of induced genes. IFN-λs act by binding to the heterodimeric IFN-λ receptor (IFNLR), activating a STAT phosphorylation-dependent signaling cascade. Thereby hundreds of IFN-stimulated genes are induced, which modulate various immune functions via complex forward and feedback loops. When compared to the well-characterized IFN-α signaling cascade, three important differences have been discovered...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28293233/the-soil-bacterium-methylococcus-capsulatus-bath-interacts-with-human-dendritic-cells-to-modulate-immune-function
#20
Stine Indrelid, Charlotte Kleiveland, René Holst, Morten Jacobsen, Tor Lea
The prevalence of inflammatory bowel disease (IBD) has increased in Western countries during the course of the twentieth century, and is evolving to be a global disease. Recently we showed that a bacterial meal of a non-commensal, non-pathogenic methanotrophic soil bacterium, Methylococcus capsulatus Bath prevents experimentally induced colitis in a murine model of IBD. The mechanism behind the effect has this far not been identified. Here, for the first time we show that M. capsulatus, a soil bacterium adheres specifically to human dendritic cells, influencing DC maturation, cytokine production, and subsequent T cell activation, proliferation and differentiation...
2017: Frontiers in Microbiology
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