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https://www.readbyqxmd.com/read/28632753/mait-cells-launch-a-rapid-robust-and-distinct-hyperinflammatory-response-to-bacterial-superantigens-and-quickly-acquire-an-anergic-phenotype-that-impedes-their-cognate-antimicrobial-function-defining-a-novel-mechanism-of-superantigen-induced-immunopathology
#1
Christopher R Shaler, Joshua Choi, Patrick T Rudak, Arash Memarnejadian, Peter A Szabo, Mauro E Tun-Abraham, Jamie Rossjohn, Alexandra J Corbett, James McCluskey, John K McCormick, Olivier Lantz, Roberto Hernandez-Alejandro, S M Mansour Haeryfar
Superantigens (SAgs) are potent exotoxins secreted by Staphylococcus aureus and Streptococcus pyogenes. They target a large fraction of T cell pools to set in motion a "cytokine storm" with severe and sometimes life-threatening consequences typically encountered in toxic shock syndrome (TSS). Given the rapidity with which TSS develops, designing timely and truly targeted therapies for this syndrome requires identification of key mediators of the cytokine storm's initial wave. Equally important, early host responses to SAgs can be accompanied or followed by a state of immunosuppression, which in turn jeopardizes the host's ability to combat and clear infections...
June 2017: PLoS Biology
https://www.readbyqxmd.com/read/28628673/multiple-tolerance-defects-contribute-to-the-breach-of-b-cell-tolerance-in-new-zealand-black-chromosome-1-congenic-mice
#2
Nan-Hua Chang, Kieran P Manion, Christina Loh, Evelyn Pau, Yuriy Baglaenko, Joan E Wither
Lupus is characterized by a loss of B cell tolerance leading to autoantibody production. In this study, we explored the mechanisms underlying this loss of tolerance using B6 congenic mice with an interval from New Zealand Black chromosome 1 (denoted c1(96-100)) sufficient for anti-nuclear antibody production. Transgenes for soluble hen egg white lysozyme (sHEL) and anti-HEL immunoglobulin were crossed onto this background and various tolerance mechanisms examined. We found that c1(96-100) mice produced increased levels of IgM and IgG anti-HEL antibodies compared to B6 mice and had higher proportions of germinal center B cells and long-lived plasma cells, suggesting a germinal center-dependent breach of B cell anergy...
2017: PloS One
https://www.readbyqxmd.com/read/28606939/transcriptional-and-epigenetic-regulation-of-t-cell-hyporesponsiveness
#3
REVIEW
Renata M Pereira, Patrick G Hogan, Anjana Rao, Gustavo J Martinez
Naive CD8(+) T cells differentiate into effector and memory cytolytic T cells (CTLs) during an acute infection. In contrast, in scenarios of persistent antigen stimulation, such as chronic infections and cancer, antigen-specific CTLs show a gradual decrease in effector function, a phenomenon that has been termed CD8(+) T cell "exhaustion" or "dysfunction." Another hyporesponsive state, termed anergy, is observed when T cells are activated in the absence of positive costimulatory signals. Among the many negative regulators induced in hyporesponsive T cells are inhibitory cell-surface receptors, such as PD-1, LAG-3, CTLA-4, and TIM-3; "checkpoint blockade" therapies that involve treatment of patients with cancer with blocking antibodies to those receptors show considerable promise in the clinic because the blocking antibodies can mitigate hyporesponsiveness and promote tumor rejection...
June 12, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28599122/respiratory-syncytial-virus-infection-compromises-asthma-tolerance-by-recruiting-interleukin-17a-producing-cells-via-ccr6-ccl20-signaling
#4
Tianyun Shi, Yanchao He, Wei Sun, Yi Wu, Ling Li, Zhijun Jie, Xiao Su
Asthma tolerance can be induced by breast-feeding or oral feeding with ovalbumin (OVA). Anergy or deletion of specific T cells and generation of T regulatory cells might contribute to this process. However, whether respiratory syncytial virus (RSV) infection would affect asthma tolerance is not very clear. Here, we first established asthma and oral tolerance mouse models and then analyzed airway hypersensitivity and asthma-related genes in the lung, CCR6-expressing IL-17A(+) cells in the lungs, hilar or mesenteric lymph nodes (HLN or MLN) among control, asthmatic, tolerized, RSV infection, and RSV-infected asthmatic and tolerized groups...
June 6, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28576496/identification-of-zinc-finger-transcription-factor-egr2-as-a-novel-acetylated-protein
#5
Kota Noritsugu, Akihiro Ito, Yoichi Nakao, Minoru Yoshida
EGR2 is a zinc finger transcription factor that regulates myelination in the peripheral nervous system and T cell anergy. The transcriptional activity of EGR2 is known to be regulated by its co-activators and/or co-repressors. Although the activity of transcription factors is generally regulated not only by interactions with co-regulators but also posttranslational modifications including acetylation, little is known about posttranslational modifications of EGR2. Here we show that EGR2 is a novel acetylated protein...
May 30, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28572627/microrna-150-modulates-intracellular-ca-2-levels-in-na%C3%A3-ve-cd8-t-cells-by-targeting-tmem20
#6
Tae-Don Kim, Hong-Ryul Jung, Sang-Hwan Seo, Se-Chan Oh, Youngho Ban, Xiaoxia Tan, Jung Min Kim, Sang Hyun Lee, Duk-Su Koh, Haiyoung Jung, Young-Jun Park, Suk Ran Yoon, Junsang Doh, Sang-Jun Ha, Inpyo Choi, Philip D Greenberg
Regulation of intracellular Ca(2+) signaling is a major determinant of CD8(+) T cell responsiveness, but the mechanisms underlying this regulation of Ca(2+) levels, especially in naïve CD8(+) T cells, are not fully defined. Here, we showed that microRNA-150 (miR-150) controls intracellular Ca(2+) levels in naïve CD8(+) T cells required for activation by suppressing TMEM20, a negative regulator of Ca(2+) extrusion. miR-150 deficiency increased TMEM20 expression, which resulted in increased intracellular Ca(2+) levels in naïve CD8(+) T cells...
June 1, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28550730/transplantation-of-aire-overexpressing-bone-marrow-derived-dendritic-cells-delays-the-onset-of-type-1-diabetes
#7
Dongbei Li, Bo Zhao, Yadong Luo, Steven Limbara, Bingjie Zhao, Xueyang Zou, Wei Yang, Yi Li
Autoimmune regulator (Aire) plays an indispensable role in maintaining central immune tolerance by promoting the ectopic expression of tissue-restricted antigens (TRAs) in medullary thymic epithelial cells (mTECs) and dendritic cells (DCs), which lead to the deletion of autoreactive T cells or the induction of Tregs and consequently prevent autoimmune disease development. Curing autoimmune diseases has always been a challenge. DC-based immunotherapy represents a new and effective method to establish tolerance...
May 24, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28507081/reversion-of-anergy-signatures-in-clonal-cd21low-b-cells-of-mixed-cryoglobulinemia-after-clearance-of-hcv-viremia
#8
Martina Del Padre, Laura Todi, Milica Mitrevski, Ramona Marrapodi, Stefania Colantuono, Massimo Fiorilli, Milvia Casato, Marcella Visentini
Hepatitis C virus (HCV) causes mixed cryoglobulinemia (MC) by driving clonal expansion of IgM(+)CD27(+) B cells. These cells display both the features of anergy induced by continual engagement of the B cell receptor (BCR), such as high expression of phosphorylated extracellular signal regulated kinase (pERK) and reduced lifespan, and of virus-specific exhaustion such as CD21(low) phenotype and defective response to ligation of BCR and Toll-like receptor 9 (TLR9). Usually MC regresses after eradication of HCV with interferon, whose immunomodulatory activity might contribute to this effect...
May 15, 2017: Blood
https://www.readbyqxmd.com/read/28500564/calcium-signaling-from-normal-b-cell-development-to-tolerance-breakdown-and-autoimmunity
#9
REVIEW
Patrice Hemon, Yves Renaudineau, Marjolaine Debant, Nelig Le Goux, Sreya Mukherjee, Wesley Brooks, Olivier Mignen
Maintenance of self-tolerance of auto-reactive lymphocytes is a fundamental mechanism to prevent the onset of autoimmune diseases. Deciphering the mechanisms involved in the deregulations leading to tolerance disruption and autoimmunity is still a major area of interest to identify new therapeutic targets and options. Ca(2+) signaling plays a major role in B cell normal development and is therefore finely tuned by B cell receptor (BCR)-dependent and independent pathways. Developmental changes in the characteristics of BCR-dependent Ca(2+) signals as well as the modulation of basal intracellular concentration ([Ca(2+)]i) contribute strongly to self-tolerance maintaining mechanisms responsible for the physical or functional elimination of autoreactive B cells such as clonal deletion, receptor editing, and anergy...
May 13, 2017: Clinical Reviews in Allergy & Immunology
https://www.readbyqxmd.com/read/28490813/leptin-receptor-antagonism-of-inkt-cell-function-a-novel-strategy-to-combat-multiple-myeloma
#10
M Favreau, E Menu, D Gaublomme, K Vanderkerken, S Faict, K Maes, E De Bruyne, S Govindarajan, M Drennan, S Van Calenbergh, X Leleu, L Zabeau, J Tavernier, K Venken, D Elewaut
A hallmark of bone marrow changes with aging is the increase in adipocyte composition, but how this impacts development of multiple myeloma (MM) is unknown. Here, we report the role of the adipokine leptin as master regulator of anti-myeloma tumor immunity by modulating the invariant natural killer T (iNKT) cell function. A marked increase in serum leptin levels and leptin receptor (LR) expression on iNKT cells in MM patients and the 5T33 murine MM model was observed. MM cells and leptin synergistically counteracted anti-tumor functionality of both murine and human iNKT cells...
May 11, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28479213/original-antigenic-sin-a-comprehensive-review
#11
REVIEW
Anup Vatti, Diana M Monsalve, Yovana Pacheco, Christopher Chang, Juan-Manuel Anaya, M Eric Gershwin
The concept of "original antigenic sin" was first proposed by Thomas Francis, Jr. in 1960. This phenomenon has the potential to rewrite what we understand about how the immune system responds to infections and its mechanistic implications on how vaccines should be designed. Antigenic sin has been demonstrated to occur in several infectious diseases in both animals and humans, including human influenza infection and dengue fever. The basis of "original antigenic sin" requires immunological memory, and our immune system ability to autocorrect...
May 5, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28436457/fasciola-hepatica-glycoconjugates-immuneregulate-dendritic-cells-through-the-dendritic-cell-specific-intercellular-adhesion-molecule-3-grabbing-non-integrin-inducing-t-cell-anergy
#12
Ernesto Rodríguez, Hakan Kalay, Verónica Noya, Natalie Brossard, Cecilia Giacomini, Yvette van Kooyk, Juan J García-Vallejo, Teresa Freire
Dendritic cell-specific ICAM-3 grabbing non-integrin (DC-SIGN) expressed on a variety of DCs, is a C-type lectin receptor that recognizes glycans on a diverse range of pathogens, including parasites. The interaction of DC-SIGN with pathogens triggers specific signaling events that modulate DC-maturation and activity and regulate T-cell activation by DCs. In this work we evaluate whether F. hepatica glycans can immune modulate DCs via DC-SIGN. We demonstrate that DC-SIGN interacts with F. hepatica glycoconjugates through mannose and fucose residues...
April 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28429719/transiently-antigen-primed-b-cells-return-to-naive-like-state-in-absence-of-t-cell-help
#13
Jackson S Turner, Matangi Marthi, Zachary L Benet, Irina Grigorova
The perspective that naive B-cell recognition of antigen in the absence of T-cell help causes cell death or anergy is supported by in vivo studies of B cells that are continuously exposed to self-antigens. However, intravital imaging suggests that early B-cell recognition of large foreign antigens may be transient. Whether B cells are tolerized or can be recruited into humoural immune responses following such encounters is not clear. Here we show that in the presence of T-cell help, single transient antigen acquisition is sufficient to recruit B cells into the germinal centre and induce memory and plasma cell responses...
April 21, 2017: Nature Communications
https://www.readbyqxmd.com/read/28421069/engineering-chimeric-antigen-receptor-t-cells-for-racing-in-solid-tumors-don-t-forget-the-fuel
#14
REVIEW
Melita Irving, Romain Vuillefroy de Silly, Kirsten Scholten, Nahzli Dilek, George Coukos
T-cells play a critical role in tumor immunity. Indeed, the presence of tumor-infiltrating lymphocytes is a predictor of favorable patient prognosis for many indications and is a requirement for responsiveness to immune checkpoint blockade therapy targeting programmed cell death 1. For tumors lacking immune infiltrate, or for which antigen processing and/or presentation has been downregulated, a promising immunotherapeutic approach is chimeric antigen receptor (CAR) T-cell therapy. CARs are hybrid receptors that link the tumor antigen specificity and affinity of an antibody-derived single-chain variable fragment with signaling endodomains associated with T-cell activation...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28414296/pd-l1-interacts-with-cd80-to-regulate-graft-versus-leukemia-activity-of-donor-cd8-t-cells
#15
Xiong Ni, Qingxiao Song, Kaniel Cassady, Ruishu Deng, Hua Jin, Mingfeng Zhang, Haidong Dong, Stephen Forman, Paul J Martin, Yuan-Zhong Chen, Jianmin Wang, Defu Zeng
Programmed death ligand-1 (PD-L1) interacts with programmed death-1 (PD-1) and the immunostimulatory molecule CD80 and functions as a checkpoint to regulate immune responses. The interaction of PD-L1 with CD80 alone has been shown to exacerbate the severity of graft-versus-host disease (GVHD), whereas costimulation of CD80 and PD-1 ameliorates GVHD. Here we have demonstrated that temporary depletion of donor CD4+ T cells early after hematopoietic cell transplantation effectively prevents GVHD while preserving strong graft-versus-leukemia (GVL) effects in allogeneic and xenogeneic murine GVHD models...
May 1, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28411047/immunodepression-after-cpb-cytokine-dynamics-and-clinics-after-pediatric-cardiac-surgery-a-prospective-trial
#16
Georgia Justus, Christoph Walker, Lisa-Maria Rosenthal, Felix Berger, Oliver Miera, Katharina Rose Luise Schmitt
BACKGROUND: Corrective surgery for congenital heart defects is known to trigger a severe immune reaction. There has been extensive research on the effects of inflammation after cardiopulmonary bypass (CPB). Interestingly, monocytes are observed to be non-responsive to stimulation with lipopolysaccharide (LPS) under these conditions, indicating a state of immunodepression, which lays the ground for second hit infections after cardiosurgery with CPB. OBJECTIVES: The aim of this prospective study was to analyze immunodepression after pediatric cardiopulmonary bypass and to differentiate the effects of monocytic anergy on postoperative outcome...
April 11, 2017: Cytokine
https://www.readbyqxmd.com/read/28408984/b-cell-tolerance-and-autoimmunity
#17
REVIEW
Takeshi Tsubata
Self-reactive B cells are tolerized at various stages of B-cell development and differentiation, including the immature B-cell stage (central tolerance) and the germinal center (GC) B-cell stage, and B-cell tolerance involves various mechanisms such as deletion, anergy, and receptor editing. Self-reactive B cells generated by random immunoglobulin variable gene rearrangements are tolerized by central tolerance and anergy in the periphery, and these processes involve apoptosis regulated by Bim, a pro-apoptotic member of the Bcl-2 family, and regulation of B-cell signaling by various phosphatases, including SHIP-1 and SHP-1...
2017: F1000Research
https://www.readbyqxmd.com/read/28393361/immune-checkpoints-and-their-inhibition-in-cancer-and-infectious-diseases
#18
REVIEW
Lydia Dyck, Kingston H G Mills
The development of chronic infections and cancer is facilitated by a variety of immune subversion mechanisms, such as the production of anti-inflammatory cytokines, induction of regulatory T (Treg) cells, and expression of immune checkpoint molecules, including CTLA-4 and PD-1. CTLA-4, expressed on T cells, interacts with CD80/CD86, thereby limiting T-cell activation and leading to anergy. PD-1 is predominantly expressed on T cells and its interaction with PD-L1 and PD-L2 expressed on antigen-presenting cells (APCs) and tumors sends a negative signal to T cells, which can lead to T-cell exhaustion...
May 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28367469/evaluation-of-regulatory-t-cells-in-patients-with-acute-and-chronic-brucellosis
#19
Ali Ganji, Ghasem Mosayebi, Ehsanollah Ghaznavi-Rad, Khadije Khosravi, Nader Zarinfar
BACKGROUND: Brucellosis is one of the most common chronic diseases, with widespread distribution. In spite of cell-mediated immunity (CMI) modulated mainly via activated T-helper type 1 (Th1) cells, brucellosis can advance to chronic disease in about 10-30% of cases. Regulatory T cells (Treg cells) are involved the immune response to brucellosis; however, their role, particularly in the change from the acute to the chronic phase, have not yet been elucidated. The main hypothesis of this study was that Treg cells play critical roles in the progression of brucellosis from the acute to the chronic phase...
April 2017: Reports of Biochemistry & Molecular Biology
https://www.readbyqxmd.com/read/28335781/tailored-design-of-nkt-stimulatory-glycolipids-for-polarization-of-immune-responses
#20
REVIEW
Jung-Tung Hung, Jing-Rong Huang, Alice L Yu
Natural killer T (NKT) cell is a distinct population of T lymphocytes that can rapidly release massive amount of Th1 and Th2 cytokines upon the engagement of their T cell receptor with glycolipids presented by CD1d. The secreted cytokines can promote cell-mediated immunity to kill tumor cells and intracellular pathogens, or suppress autoreactive immune cells in autoimmune diseases. Thus, NKT cell is an attractive target for developing new therapeutics to manipulate immune system. The best-known glycolipid to activate NKT cells is α-galactosylceramide (α-GalCer), which has been used as a prototype for designing new NKT stimulatory glycolipids...
March 23, 2017: Journal of Biomedical Science
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