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T cell activation

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https://www.readbyqxmd.com/read/28329703/successful-and-maladaptive-t-cell-aging
#1
REVIEW
Jörg J Goronzy, Cornelia M Weyand
Throughout life, the T cell system adapts to shifting resources and demands, resulting in a fundamentally restructured immune system in older individuals. Here we review the cellular and molecular features of an aged immune system and discuss the trade-offs inherent to these adaptive mechanisms. Processes include homeostatic proliferation that maintains compartment size at the expense of partial loss in stemness and incomplete differentiation and the activation of negative regulatory programs, which constrain effector T cell expansion and prevent increasing oligoclonality but also interfere with memory cell generation...
March 21, 2017: Immunity
https://www.readbyqxmd.com/read/28329691/myocardial-infarction-primes-autoreactive-t-cells-through-activation-of-dendritic-cells
#2
Katrien Van der Borght, Charlotte L Scott, Veronika Nindl, Ann Bouché, Liesbet Martens, Dorine Sichien, Justine Van Moorleghem, Manon Vanheerswynghels, Sofie De Prijck, Yvan Saeys, Burkhard Ludewig, Thierry Gillebert, Martin Guilliams, Peter Carmeliet, Bart N Lambrecht
Peripheral tolerance is crucial for avoiding activation of self-reactive T cells to tissue-restricted antigens. Sterile tissue injury can break peripheral tolerance, but it is unclear how autoreactive T cells get activated in response to self. An example of a sterile injury is myocardial infarction (MI). We hypothesized that tissue necrosis is an activator of dendritic cells (DCs), which control tolerance to self-antigens. DC subsets of a murine healthy heart consisted of IRF8-dependent conventional (c)DC1, IRF4-dependent cDC2, and monocyte-derived DCs...
March 21, 2017: Cell Reports
https://www.readbyqxmd.com/read/28329675/trimethylation-and-acetylation-of-%C3%AE-catenin-at-lysine-49-represent-key-elements-in-esc-pluripotency
#3
Katrin Hoffmeyer, Dirk Junghans, Benoit Kanzler, Rolf Kemler
Wnt/β-catenin signaling is required for embryonic stem cell (ESC) pluripotency by inducing mesodermal differentiation and inhibiting neuronal differentiation; however, how β-catenin counter-regulates these differentiation pathways is unknown. Here, we show that lysine 49 (K49) of β-catenin is trimethylated (β-catMe3) by Ezh2 or acetylated (β-catAc) by Cbp. Significantly, β-catMe3 acts as a transcriptional co-repressor of the neuronal differentiation genes sox1 and sox3, whereas β-catAc acts as a transcriptional co-activator of the key mesodermal differentiation gene t-brachyury (t-bra)...
March 21, 2017: Cell Reports
https://www.readbyqxmd.com/read/28329310/immunologic-pathways-that-predict-mortality-in-hiv-infected-ugandans-initiating-art
#4
Sulggi Lee, Helen Byakwaga, Yap Boum, Tricia H Burdo, Kenneth C Williams, Michael M Lederman, Yong Huang, Russell P Tracy, Huyen Cao, Jessica E Haberer, Annet Kembabazi, David R Bangsberg, Jeffrey N Martin, Peter W Hunt
Plasma kynurenine/tryptophan (KT) ratio, a marker of adaptive immune defects, strongly predicts mortality during treated HIV disease in Ugandans compared to U.S.-based populations, Here, KT ratio, and T cell and plasma biomarkers of immune activation were measured among 535 HIV-infected Ugandans prior to ART initiation and at month 6 of viral suppression. Month 6 KT ratio (aHR=2.74), sCD14 (aHR=2.32), IL-6 (aHR=2.34), and D dimer (aHR=1.95) were associated with mortality occurring ≥6 months after ART initiation, KT ratio remained significantly predictive of mortality even after adjustment for the additional biomarkers, suggesting an independent contribution to clinical outcomes in resource-limited settings...
March 1, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28329286/short-course-tlr9-agonist-treatment-impacts-innate-immunity-and-plasma-viremia-in-individuals-with-hiv-infection
#5
Line Vibholm, Mariane H Schleimann, Jesper F Højen, Thomas Benfield, Rasmus Offersen, Katrine Rasmussen, Rikke Olesen, Anders Dige, Jørgen Agnholt, Judith Grau, Maria Buzon, Burghardt Wittig, Mathias Lichterfeld, Andreas Munk Petersen, Xutao Deng, Mohammed Abdel-Mohsen, Satish K Pillai, Sofie Rutsaert, Wim Trypsteen, Ward De Spiegelaere, Linos Vandekerchove, Lars Østergaard, Thomas A Rasmussen, Paul W Denton, Martin Tolstrup, Ole S Søgaard
Background: Treatment with latency reversing agents (LRA) enhances HIV-1 transcription in vivo but only leads to modest reductions in the size of the reservoir, possibly due to insufficient immune-mediated elimination of infected cells. We hypothesized that a single drug molecule - a novel toll-like receptor 9 (TLR9) agonist, MGN1703 - could function as an enhancer of innate immunity and an LRA in vivo. Methods: We conducted a single-arm, open-label study, where 15 virologically suppressed HIV-1 infected individuals on antiretroviral therapy received 60 mg MGN1703 s...
March 9, 2017: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
https://www.readbyqxmd.com/read/28329187/bumped-kinase-inhibitors-for-therapy-of-cryptosporidiosis
#6
Matthew A Hulverson, Sumiti Vinayak, Ryan Choi, Deborah A Schaefer, Alejandro Castellanos-Gonzalez, Rama S R Vidadala, Carrie F Brooks, Gillian T Herbert, Dana P Betzer, Grant R Whitman, Hayley N Sparks, Samuel L M Arnold, Kasey L Rivas, Lynn K Barrett, A Clinton White, Maly Dustin J, Michael W Riggs, Boris Striepen, Wesley C Van Voorhis, Kayode K Ojo
Bumped kinase inhibitors (BKIs) of Cryptosporidium parvum calcium-dependent protein kinase 1 (CpCDPK1) are leading candidates for treatment of cryptosporidiosis diarrhea. Potential cardiotoxicity related to anti-human ether-à-go-go potassium channel (hERG) activity of the first generation anti-Cryptosporidium BKIs triggered further testing for efficacy. A luminescence assay adapted for high-throughput screening was used to measure inhibitory activities of BKIs on in vitro C. parvum. Furthermore, neonatal and interferon-γ knockout mouse models of C...
March 3, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28329119/stratification-of-latent-tuberculosis-infection-by-cellular-immune-profiling
#7
Alice Halliday, Hilary Whitworth, Sherine Hermagild Kottoor, Umar Niazi, Sarah Menzies, Heinke Kunst, Samuel Bremang, Amarjit Badhan, Peter Beverley, Onn Min Kon, Ajit Lalvani
Background: Recently-acquired and remotely-acquired latent tuberculosis (TB) infection (LTBI) are clinically indistinguishable, yet recent acquisition of infection is the greatest risk factor for progression to active TB (ATB) in immunocompetent individuals. We aimed to evaluate the ability of cellular immune signatures which differ between ATB and LTBI, to distinguish recently from remotely acquired LTBI. Methods: Fifty-nine individuals were recruited: ATB (n=20); recent LTBI (n=19); remote LTBI (n=20)...
February 28, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28329009/the-expression-and-localization-of-rnase-and-rnase-inhibitor-in-blood-cells-and-vascular-endothelial-cells-in-homeostasis-of-the-vascular-system
#8
Ayaka Ohashi, Aya Murata, Yuichiro Cho, Shizuko Ichinose, Yuriko Sakamaki, Miwako Nishio, Osamu Hoshi, Silvia Fischer, Klaus T Preissner, Takatoshi Koyama
RNA may be released from vascular cells including endothelial cells in the event of injury and in vascular disease. Extracellular RNAs have been recognized as novel procoagulant and permeability-increasing factors. Extracellular RNA may function as inflammatory host alarm signals that serve to amplify the defense mechanism, but it may provide important links to thrombus formation. Extracellular RNA is degraded by RNase. We propose that RNase and its inhibitor RNase inhibitor (RI) act as modulators of homeostasis in the vasculature to control the functions of extracellular RNA...
2017: PloS One
https://www.readbyqxmd.com/read/28328926/frequency-and-role-of-nkp46-and-nkg2a-in-hepatitis-b-virus-infection
#9
Teppei Yoshioka, Tomohide Tatsumi, Takuya Miyagi, Kaori Mukai, Kumiko Nishio, Akira Nishio, Yoshinobu Yokoyama, Takahiro Suda, Tadashi Kegasawa, Minoru Shigekawa, Hayato Hikita, Ryotaro Sakamori, Tetsuo Takehara
BACKGROUND AND AIM: Natural Killer (NK) cells are involved in the control of viral infection. However, the role of NK cells in chronic hepatitis B (CHB) remains unclear. This study investigated the frequencies and roles of NK cells in CHB, with a focus on activating receptor NKp46 and inhibitory receptor NKG2A. PATIENTS/METHOD: Peripheral blood lymphocytes were obtained from 71 CHB patients and 37 healthy subjects (HS). The expressions of NKp46 and NKG2A were analyzed using flow cytometry...
2017: PloS One
https://www.readbyqxmd.com/read/28328797/activation-senescence-and-inflammation-markers-in-hiv-patients-association-with-renal-function
#10
Alexandra Ozanne, Pierre Duffau, Frédéric-Antoine Dauchy, Claire Rigothier, Cécile Terrien, Estibaliz Lazaro, Charles Cazanave, Sylvie Lawson-Ayayi, Fabrice Bonnet, Patrick Blanco, Linda Wittkop, Isabelle Pellegrin
OBJECTIVES: To assess the association between immune-activation (IA), immune-senescence (IS), inflammation biomarkers and renal function measured by estimated glomerular function rate (eGFR) at inclusion and its evolution over a 3-years follow-up in HIV-infected patients with undetectable viral load. DESIGN: The CIADIS (Chronic Immune Activation anD Senescence) sub-study consecutively included patients between October 2011 and May 2013 enrolled in the ANRS CO3 Aquitaine observational cohort...
March 21, 2017: AIDS
https://www.readbyqxmd.com/read/28328794/hcv-drives-increased-type-i-ifn-associated-impairments-associated-to-fibrosis-severity-in-art-treated-hiv-1-hcv-coinfected-individuals
#11
Morgane Griesbeck, Marc-Antoine Valantin, Karine Lacombe, Assia Samri-Hassimi, Julie Bottero, Catherine Blanc, Zineb Sbihi, Rima Zoorob, Christine Katlama, Marguerite Guiguet, Marcus Altfeld, Brigitte Autran
BACKGROUND: Viral coinfections might contribute to the increased immune activation and inflammation that persist in ART-treated HIV-1 patients. We investigated whether the HCV co-infection contributes to such alterations by impairing the pDC IFNα/TLR7 pathway in a highly homogeneous group of ART-treated HIV-1-HCV co-infected patients. METHODS: Twenty nine HIV-1-infected patients with fully suppressive ART were included, fifteen of whom being HCV co-infected with mild to moderate fibrosis and matched for their HIV-1 disease, and thirteen control healthy donors...
March 21, 2017: AIDS
https://www.readbyqxmd.com/read/28328682/early-tranexamic-acid-administration-ameliorates-the-endotheliopathy-of-trauma-and-shock-in-an-in-vitro-model
#12
Lawrence N Diebel, Jonathan V Martin, David M Liberati
BACKGROUND: Systemic vascular endothelial injury is a consequence of trauma-hemorrhagic shock (T/HS) which results in disturbances of coagulation, inflammation and endothelial barrier integrity. The effect of T/HS on the endothelium (Endotheliopathy of Trauma)[EoT] is of intense research interest and may lead to EoT directed therapies. Administration of tranexamic acid (TXA) in trauma patients is associated with a survival benefit and fewer complications if given early after injury. Mechanisms for this protective effect include the anti-fibrinolytic and anti-inflammatory effects of TXA...
March 21, 2017: Journal of Trauma and Acute Care Surgery
https://www.readbyqxmd.com/read/28328614/a-newborn-with-familial-hemophagocytic-lymphohistiocytosis-complicated-with-transfusion-associated-graft-versus-host-disease
#13
Ahmet Ozdemir, Tamer Gunes, Samuel C C Chiang, Ekrem Unal
Hemophagocytic lymphohistiocytosis (HLH) is characterized by activation of cytotoxic T and natural killer (NK) cells, and macrophages related to a spectrum of hyperinflammatory disorders. The clinical findings mainly include high fever, cytopenia, splenomegaly, phagocytosis, and proliferation of histiocytes in lymphoreticular tissue. To the best of our knowledge, transfusion-associated graft versus host disease (TA-GVHD) in a 13-day old male newborn with HLH is being reported first time in the literature. The aim of this report was to emphasize the importance of blood products irradiation in the prevention of the development of graft versus host disease especially among high-risk subjects such as newborns with HLH...
March 21, 2017: Journal of Pediatric Hematology/oncology
https://www.readbyqxmd.com/read/28328116/brain-morphology-in-children-with-nevoid-basal-cell-carcinoma-syndrome
#14
Tadashi Shiohama, Katsunori Fujii, Toshiyuki Miyashita, Hiromi Mizuochi, Hideki Uchikawa, Naoki Shimojo
Brain morphology is tightly regulated by diverse signaling pathways. Hedgehog signaling is a candidate pathway considered responsible for regulating brain morphology. Nevoid basal cell carcinoma syndrome (NBCCS), caused by a PTCH1 mutation in the hedgehog signaling pathway, occasionally exhibits macrocephaly and medulloblastoma. Although cerebellar enlargement occurs in ptch1 heterozygous-deficient mice, its impact on human brain development remains unknown. We investigated the brain morphological characteristics of children with NBCCS...
April 2017: American Journal of Medical Genetics. Part A
https://www.readbyqxmd.com/read/28327905/phase-ii-study-of-idelalisib-a-selective-inhibitor-of-pi3k%C3%AE-for-relapsed-refractory-classical-hodgkin-lymphoma
#15
A K Gopal, M A Fanale, C H Moskowitz, A R Shustov, S Mitra, W Ye, A Younes, A J Moskowitz
Background: The phosphatidylinositol-3-kinase delta (PI3Kδ) inhibitor idelalisib has been shown to block downstream intracellular signaling, reduce the production of prosurvival chemokines and induce apoptosis in classical Hodgkin lymphoma (HL) cell lines. It has also been shown to inhibit regulatory T cells and myeloid-derived suppressor cells in other tumor models. We hypothesized that inhibiting PI3Kδ would have both direct and indirect antitumor effects by directly targeting the malignant cells as well as modulating the inflammatory microenvironment...
January 24, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28327619/il-36%C3%AE-signaling-controls-the-induced-regulatory-t-cell-th9-cell-balance-via-nf%C3%AE%C2%BAb-activation-and-stat-transcription-factors
#16
A Harusato, H Abo, V L Ngo, S W Yi, K Mitsutake, S Osuka, J E Kohlmeier, J D Li, A T Gewirtz, A Nusrat, T L Denning
Regulatory and effector T helper (Th) cells are abundant at mucosal surfaces, especially in the intestine, where they control the critical balance between tolerance and inflammation. However, the key factors that reciprocally dictate differentiation along these specific lineages remain incompletely understood. Here we report that the interleukin-1 (IL-1) family member IL-36γ signals through IL-36 receptor, myeloid differentiation primary response gene 88, and nuclear factor-κBp50 in CD4(+) T cells to potently inhibit Foxp3-expressing induced regulatory T cell (Treg) development, while concomitantly promoting the differentiation of Th9 cells via a IL-2-STAT5- (signal transducer and activator of transcription factor 5) and IL-4-STAT6-dependent pathway...
March 22, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/28327612/endogenous-opioids-regulate-moment-to-moment-neuronal-communication-and-excitability
#17
Bryony L Winters, Gabrielle C Gregoriou, Sarah A Kissiwaa, Oliver A Wells, Danashi I Medagoda, Sam M Hermes, Neil T Burford, Andrew Alt, Sue A Aicher, Elena E Bagley
Fear and emotional learning are modulated by endogenous opioids but the cellular basis for this is unknown. The intercalated cells (ITCs) gate amygdala output and thus regulate the fear response. Here we find endogenous opioids are released by synaptic stimulation to act via two distinct mechanisms within the main ITC cluster. Endogenously released opioids inhibit glutamate release through the δ-opioid receptor (DOR), an effect potentiated by a DOR-positive allosteric modulator. Postsynaptically, the opioids activate a potassium conductance through the μ-opioid receptor (MOR), suggesting for the first time that endogenously released opioids directly regulate neuronal excitability...
March 22, 2017: Nature Communications
https://www.readbyqxmd.com/read/28327575/analysis-of-exome-data-for-4293-trios-suggests-gpi-anchor-biogenesis-defects-are-a-rare-cause-of-developmental-disorders
#18
Alistair T Pagnamenta, Yoshiko Murakami, John M Taylor, Consuelo Anzilotti, Malcolm F Howard, Venessa Miller, Diana S Johnson, Shereen Tadros, Sahar Mansour, I Karen Temple, Rachel Firth, Elisabeth Rosser, Rachel E Harrison, Bronwen Kerr, Niko Popitsch, Taroh Kinoshita, Jenny C Taylor, Usha Kini
Over 150 different proteins attach to the plasma membrane using glycosylphosphatidylinositol (GPI) anchors. Mutations in 18 genes that encode components of GPI-anchor biogenesis result in a phenotypic spectrum that includes learning disability, epilepsy, microcephaly, congenital malformations and mild dysmorphic features. To determine the incidence of GPI-anchor defects, we analysed the exome data from 4293 parent-child trios recruited to the Deciphering Developmental Disorders (DDD) study. All probands recruited had a neurodevelopmental disorder...
March 22, 2017: European Journal of Human Genetics: EJHG
https://www.readbyqxmd.com/read/28327534/the-anti-allergic-rhinitis-effect-of-traditional-chinese-medicine-of-shenqi-by-regulating-mast-cell-degranulation-and-th1-th2-cytokine-balance
#19
Yang-Yang Shao, Yi-Ming Zhou, Min Hu, Jin-Ze Li, Cheng-Juan Chen, Yong-Jiang Wang, Xiao-Yun Shi, Wen-Jie Wang, Tian-Tai Zhang
Shenqi is a traditional Chinese polyherbal medicine has been widely used for the treatment of allergic rhinitis (AR). The aim of this study was to investigate the anti-allergic rhinitis activity of Shenqi and explore its underlying molecular mechanism. Ovalbumin (OVA)-induced allergic rhinitis rat model was used to evaluate the anti-allergic rhinitis effect of Shenqi. The effect of Shenqi on IgE-mediated degranulation was measured using rat basophilic leukemia (RBL-2H3) cells. Primary spleen lymphocytes were isolated to investigate the anti-allergic mechanism of Shenqi by detecting the expression of transcription factors via Western blot and the level of cytokines (IL-4 and IFN-γ) via ELISA...
March 22, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28327518/myeloid-c-type-lectin-receptors-in-viral-recognition-and-antiviral-immunity
#20
REVIEW
João T Monteiro, Bernd Lepenies
Recognition of viral glycans by pattern recognition receptors (PRRs) in innate immunity contributes to antiviral immune responses. C-type lectin receptors (CLRs) are PRRs capable of sensing glycans present in viral pathogens to activate antiviral immune responses such as phagocytosis, antigen processing and presentation, and subsequent T cell activation. The ability of CLRs to elicit and shape adaptive immunity plays a critical role in the inhibition of viral spread within the host. However, certain viruses exploit CLRs for viral entry into host cells to avoid immune recognition...
March 22, 2017: Viruses
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