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https://www.readbyqxmd.com/read/29908067/effects-of-type-i-interferons-in-malaria
#1
REVIEW
Ismail Sebina, Ashraful Haque
Type I interferons are a family of cytokines with a wide range of biological activities including anti-viral and immune-regulatory functions. Here, we focus on the protozoan parasitic disease, malaria, and examine the effects of type I IFN-signalling during Plasmodium infection of humans and experimental mice. Since the 1960's, there have been many studies in this area, but a simple explanation for the role of type I IFN has not emerged. Although epidemiological data are consistent with roles for type I IFN in influencing malaria disease severity, functional proof of this remains sparse in humans...
June 16, 2018: Immunology
https://www.readbyqxmd.com/read/29907762/duplication-of-a-germline-promoter-downstream-of-the-igh-3-regulatory-region-impairs-class-switch-recombination
#2
Joana M Santos, Fatima-Zohra Braikia, Chloé Oudinet, Dania Haddad, Caroline Conte, Audrey Dauba, Ahmed Amine Khamlichi
During an adaptive immune response, B cells can change their surface immunoglobulins from IgM to IgG, IgE or IgA through a process called class switch recombination (CSR). Switching is preceded by inducible non-coding germline transcription (GLT) of the selected constant gene(s), which is largely controlled by a super-enhancer called the 3' regulatory region (3'RR). Despite intense efforts, the precise mechanisms that regulate GLT are still elusive. In order to gain additional insights into these mechanisms, we analyzed GLT and CSR in mutant B cells carrying a duplication of the promoter of the α constant gene (Iα) downstream of 3'RR...
June 15, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29907552/beyond-maximum-grade-modernising-the-assessment-and-reporting-of-adverse-events-in-haematological-malignancies
#3
REVIEW
Gita Thanarajasingam, Lori M Minasian, Frederic Baron, Franco Cavalli, R Angelo De Claro, Amylou C Dueck, Tarec C El-Galaly, Neil Everest, Jan Geissler, Christian Gisselbrecht, John Gribben, Mary Horowitz, S Percy Ivy, Caron A Jacobson, Armand Keating, Paul G Kluetz, Aviva Krauss, Yok Lam Kwong, Richard F Little, Francois-Xavier Mahon, Matthew J Matasar, María-Victoria Mateos, Kristen McCullough, Robert S Miller, Mohamad Mohty, Philippe Moreau, Lindsay M Morton, Sumimasa Nagai, Simon Rule, Jeff Sloan, Pieter Sonneveld, Carrie A Thompson, Kyriaki Tzogani, Flora E van Leeuwen, Galina Velikova, Diego Villa, John R Wingard, Sophie Wintrich, John F Seymour, Thomas M Habermann
Tremendous progress in treatment and outcomes has been achieved across the whole range of haematological malignancies in the past two decades. Although cure rates for aggressive malignancies have increased, nowhere has progress been more impactful than in the management of typically incurable forms of haematological cancer. Population-based data have shown that 5-year survival for patients with chronic myelogenous and chronic lymphocytic leukaemia, indolent B-cell lymphomas, and multiple myeloma has improved markedly...
June 12, 2018: Lancet Haematology
https://www.readbyqxmd.com/read/29907235/rapid-valproic-acid-induced-modulation-of-the-traumatic-proteome-in-a-porcine-model-of-traumatic-brain-injury-and-hemorrhagic-shock
#4
Michael Weykamp, Vahagn C Nikolian, Isabel S Dennahy, Gerald A Higgins, Patrick E Georgoff, Henriette Remmer, Mohamed H Ghandour, Hasan B Alam
BACKGROUND: Histone deacetylase inhibitors such as valproic acid (VPA) improve survival in lethal models of hemorrhagic shock and polytrauma. Although VPA is known to modulate transcription, its ability to reduce mortality within minutes of administration suggests involvement of a rapid, posttranslational mechanism. We hypothesized that VPA treatment would cause proteomic changes within minutes of treatment including quantitative and/or posttranslational differences in structural and/or effector proteins...
August 2018: Journal of Surgical Research
https://www.readbyqxmd.com/read/29906486/pathophysiological-consequences-of-isoform-specific-ip-3-receptor-mutations
#5
REVIEW
Martijn Kerkhofs, Bruno Seitaj, Hristina Ivanova, Giovanni Monaco, Geert Bultynck, Jan B Parys
Ca2+ signaling governs a diverse range of cellular processes and, as such, is subject to tight regulation. A main component of the complex intracellular Ca2+ -signaling network is the inositol 1,4,5-trisphosphate (IP3 ) receptor (IP3 R), a tetrameric channel that mediates Ca2+ release from the endoplasmic reticulum (ER) in response to IP3 . IP3 R function is controlled by a myriad of factors, such as Ca2+ , ATP, kinases and phosphatases and a plethora of accessory and regulatory proteins. Further complexity in IP3 R-mediated Ca2+ signaling is the result of the existence of three main isoforms (IP3 R1, IP3 R2 and IP3 R3) that display distinct functional characteristics and properties...
June 12, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29904934/common-gamma-chain-cytokines-promote-regulatory-t-cell-development-and-survival-at-the-cd4-cd8-stage-in-the-human-thymus
#6
Reetta Vanhanen, Anni Tuulasvaara, Joonatan Mattila, Tommi Pätilä, T Petteri Arstila
Thymic commitment of human FOXP3+ regulatory T cells begins at the double positive (DP) CD4+ CD8+ stage. In the current study we show that interleukin-2 promotes the development of FOXP3+ thymocytes and enhances their survival at the DP phase. IL-2 increases the frequency of FOXP3+ cells and promotes the Treg phenotype after TCR-mediated positive selection at the most mature DP stage. However, it has no effect on FOXP3+ cells at the earlier maturation steps before positive selection. DP FOXP3+ are highly susceptible to cell death but IL-2 promotes their survival...
June 15, 2018: Scandinavian Journal of Immunology
https://www.readbyqxmd.com/read/29904386/costimulatory-function-of-cd58-cd2-interaction-in-adaptive-humoral-immunity-in-a-zebrafish-model
#7
Tong Shao, Wei Shi, Jia-Yu Zheng, Xiao-Xiao Xu, Ai-Fu Lin, Li-Xin Xiang, Jian-Zhong Shao
CD58 and CD2 have long been known as a pair of reciprocal adhesion molecules involved in the immune modulations of CD8+ T and NK-mediated cellular immunity in humans and several other mammals. However, the functional roles of CD58 and CD2 in CD4+ T-mediated adaptive humoral immunity remain poorly defined. Moreover, the current functional observations of CD58 and CD2 were mainly acquired from in vitro assays, and in vivo investigation is greatly limited due to the absence of a Cd58 homology in murine models...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29904381/the-calcineurin-inhibitor-tacrolimus-specifically-suppresses-human-t-follicular-helper-cells
#8
Elizabeth F Wallin, Danika L Hill, Michelle A Linterman, Kathryn J Wood
Background: T follicular helper (Tfh) cells are key players in the production of antibody-producing B cells via the germinal center reaction. Therapeutic strategies targeting Tfh cells are important where antibody formation is implicated in disease, such as transplant rejection and autoimmune diseases. We investigated the impact of the immunosuppressive agent tacrolimus on human Tfh cell differentiation and function in transplant recipients. Methods: Paired blood and lymph node (LN) samples were obtained from 61 transplant recipients immediately prior to organ implantation...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29904273/fgf23-and-fetuin-a-interaction-in-the-liver-and-in-the-circulation
#9
Deborah Mattinzoli, Masami Ikehata, Koji Tsugawa, Carlo M Alfieri, Paola Dongiovanni, Elena Trombetta, Luca Valenti, Aldamaria Puliti, Lorenza Lazzari, Piergiorgio Messa
Recently it has been demonstrated that Fetuin-A, an anti-inflammatory protein synthesized by the liver, is produced also in bone by an FGF23-regulated pathway. FGF23 has been also demonstrated to induce inflammatory cytokine production in the liver. This study aimed to explore if FGF23 plays a role in the Fetuin-A production in the liver cells too and the possible relationships with FGF23 pro-inflammatory effects. FGF23 and Fetuin-A were studied in liver, kidney and in plasma with immunochemistry, immunoprecipitation, western blot, chromatin immunoprecipitation, duolink, ELISA, qrtPCR methodology...
2018: International Journal of Biological Sciences
https://www.readbyqxmd.com/read/29904021/overcoming-resistance-of-human-non-hodgkin-s-lymphoma-to-cd19-car-ctl-therapy-by-celecoxib-and-histone-deacetylase-inhibitors
#10
Antoni Xavier Torres-Collado, Ali R Jazirehi
Patients with B-cell non-Hodgkin’s lymphoma (B-NHL) who fail to respond to first-line treatment regimens or develop resistance, exhibit poor prognosis. This signifies the need to develop alternative treatment strategies. CD19-chimeric antigen receptor (CAR) T cell-redirected immunotherapy is an attractive and novel option, which has shown encouraging outcomes in phase I clinical trials of relapsed/refractory NHL. However, the underlying mechanisms of, and approaches to overcome, acquired anti-CD19CAR CD8⁺ T cells (CTL)-resistance in NHL remain elusive...
June 14, 2018: Cancers
https://www.readbyqxmd.com/read/29903725/human-primitive-brain-displays-negative-mitochondrial-nuclear-expression-correlation-of-respiratory-genes
#11
Gilad Barshad, Amit Blumberg, Tal Cohen, Dan Mishmar
Oxidative phosphorylation (OXPHOS), a fundamental energy source in all human tissues, requires interactions between mitochondrial (mtDNA) and nuclear (nDNA)-encoded protein subunits. Although such interactions are fundamental to OXPHOS, bi-genomic co-regulation is poorly understood. To address this question, we analyzed ~8,500 RNA-seq experiments from 48 human body sites. Despite well-known variation in mitochondrial activity, quantity and morphology, we found overall positive mtDNA-nDNA OXPHOS genes' co-expression across human tissues...
June 14, 2018: Genome Research
https://www.readbyqxmd.com/read/29902868/mir-146-promotes-hbv-replication-and-expression-by-targeting-zeb2
#12
Yanjing Wang, Yuanyuan Li
Hepatitis B virus (HBV) is associated with the development of a wide spectrum of liver diseases. The involvement of miRNAs in HBV replication is being gradually identified. Among these miRNAs, miR-146a expression was found to be positively correlated with HBV replication levels. However, the regulatory relationship between miR-146a and HBV replication is still unclear. In the present study, miR-146a was upregulated in HBV-expressing HepG2.2.15 cells compared with HepG2 cells. Overexpression of miR-146a or knockdown of Zinc finger E-box-binding homeobox 2 (ZEB2) promoted HBV replication and expression, while downregulation of miR-146a or overexpression of ZEB2 suppressed HBV replication and expression...
March 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29902483/cd46-is-a-potent-co-stimulatory-receptor-for-expansion-of-human-ifn-%C3%AE-producing-cd8-t-cells
#13
Aida S Hansen, Josefine Slater, Mette Biltoft, Bettina B Bundgaard, Bjarne K Møller, Per Höllsberg
Similar to CD4+ T cells, precursor CD8+ T cells are thought to depend on a co-stimulatory signal through CD28 for proliferation and differentiation into effector cells. CD46 is another co-stimulatory receptor that promotes differentiation of CD4+ T-helper cells type 1 (Th1 cells) into a regulatory phenotype with a switch from IFN-γ towards IL-10-secretion over time. Whether CD46 exerts a similar function on CD8+ T cells remains to be fully elucidated. Here, we demonstrate that CD46 co-stimulation induced secretion of IFN-γ as well as expansion of IFN-γ-secreting CD8+ T cells...
June 11, 2018: Immunology Letters
https://www.readbyqxmd.com/read/29901635/rapamycin-treatment-for-amyotrophic-lateral-sclerosis-protocol-for-a-phase-ii-randomized-double-blind-placebo-controlled-multicenter-clinical-trial-rap-als-trial
#14
Jessica Mandrioli, Roberto D'Amico, Elisabetta Zucchi, Annalisa Gessani, Nicola Fini, Antonio Fasano, Claudia Caponnetto, Adriano Chiò, Eleonora Dalla Bella, Christian Lunetta, Letizia Mazzini, Kalliopi Marinou, Gianni Sorarù, Sara de Biasi, Domenico Lo Tartaro, Marcello Pinti, Andrea Cossarizza
INTRODUCTION: Misfolded aggregated proteins and neuroinflammation significantly contribute to amyotrophic lateral sclerosis (ALS) pathogenesis, hence representing therapeutic targets to modify disease expression. Rapamycin inhibits mechanistic target of Rapamycin (mTOR) pathway and enhances autophagy with demonstrated beneficial effects in neurodegeneration in cell line and animal models, improving phenotype in SQSTM1 zebrafish, in Drosophila model of ALS-TDP, and in the TDP43 mouse model, in which it reduced neuronal loss and TDP43 inclusions...
June 2018: Medicine (Baltimore)
https://www.readbyqxmd.com/read/29901571/indoleamine-2-3-dioxygenase-in-non-small-cell-lung-cancer-a-targetable-mechanism-of-immune-resistance-frequently-coexpressed-with-pd-l1
#15
Ashley Volaric, Ryan Gentzler, Richard Hall, James H Mehaffey, Edward B Stelow, Timothy N Bullock, Linda W Martin, Anne M Mills
The immune regulatory enzyme indoleamine-2,3-dioxygenase (IDO-1) suppresses T cell responses and may reduce efficacy of therapies targeting immune checkpoints such as programmed death receptor-1/programmed death ligand-1 (PD-1/PD-L1). Early phase clinical trials combining IDO-1 and PD-1/PD-L1 inhibitors have shown some promise in non-small cell lung cancers (NSCLCs). However, the coexpression of IDO-1 and PD-L1 has not been thoroughly investigated, and the potential for IDO-1 immunohistochemical expression as a therapeutic biomarker is unknown...
June 12, 2018: American Journal of Surgical Pathology
https://www.readbyqxmd.com/read/29900065/the-immune-checkpoint-protein-pd-l1-induces-and-maintains-regulatory-t-cells-in-glioblastoma
#16
Joseph DiDomenico, Jonathan B Lamano, Daniel Oyon, Yuping Li, Dorina Veliceasa, Gurvinder Kaur, Leonel Ampie, Winward Choy, Jason B Lamano, Orin Bloch
Glioblastoma (GBM) promotes immunosuppression through upregulation of PD-L1 and regulatory T cell (Treg) expansion, but the association of these suppressive factors has not been well elucidated. Here, we investigate a role of PD-L1 in expanding Tregs and the value of targeting the PD-1 receptor to inhibit Treg expansion. Quantitative RNA sequencing data from The Cancer Genome Atlas were evaluated for an association between CD274 and FOXP3 transcript expressions and impact of FOXP3 on clinical outcomes. Peripheral leukocytes from patients with newly diagnosed GBM were profiled for PD-L1+ myeloid expressions and Treg abundance...
2018: Oncoimmunology
https://www.readbyqxmd.com/read/29900058/optimized-dendritic-cell-vaccination-induces-potent-cd8-t-cell-responses-and-anti-tumor-effects-in-transgenic-mouse-melanoma-models
#17
Mareike Grees, Adi Sharbi-Yunger, Christos Evangelou, Daniel Baumann, Gal Cafri, Esther Tzehoval, Stefan B Eichmüller, Rienk Offringa, Jochen Utikal, Lea Eisenbach, Viktor Umansky
Despite melanoma immunogenicity and remarkable therapeutic effects of negative immune checkpoint inhibitors, a significant fraction of patients does not respond to current treatments. This could be due to limitations in tumor immunogenicity and profound immunosuppression in the melanoma microenvironment. Moreover, insufficient tumor antigen processing and presentation by dendritic cells (DC) may hamper the development of tumor-specific T cells. Using two genetically engineered mouse melanoma models ( RET and BRAFV600E transgenic mice), in which checkpoint inhibitor therapy alone is not efficacious, we performed proof-of-concept studies with an improved, multivalent DC vaccination strategy based on our recently developed genetic mRNA cancer vaccines...
2018: Oncoimmunology
https://www.readbyqxmd.com/read/29900049/prognostic-implications-of-tumor-infiltrating-macrophages-m2-macrophages-regulatory-t-cells-and-indoleamine-2-3-dioxygenase-positive-cells-in-primary-diffuse-large-b-cell-lymphoma-of-the-central-nervous-system
#18
Soo Jeong Nam, Sehui Kim, Dohee Kwon, Hannah Kim, Soyeon Kim, Eunyoung Lee, Tae Min Kim, Dae Seog Heo, Sung Hye Park, Megan S Lim, Chul Woo Kim, Yoon Kyung Jeon
Primary diffuse large B-cell lymphoma of the central nervous system (CNS-DLBCL) is an aggressive disease with a poor prognosis. The status of the tumor immune microenvironment in CNS-DLBCL remains unclear. We investigated the prognostic implications of tumor-associated macrophages (TAMs), regulatory T-cells (Tregs), and indoleamine 2,3-dioxygenase (IDO)+ cells in primary CNS-DLBCL (n = 114) by immunohistochemical analysis. The numbers of tumor-infiltrating immune cells, including CD68+ TAMs, CD163+ or CD204+ M2 macrophages, FOXP3+ Tregs, and IDO+ cells were all significantly lower in CNS-DLBCL versus systemic DLBCL (n = 165; all P < 0...
2018: Oncoimmunology
https://www.readbyqxmd.com/read/29900006/model-based-identification-of-tnf%C3%AE-induced-ikk%C3%AE-mediated-and-i%C3%AE%C2%BAb%C3%AE-mediated-regulation-of-nf%C3%AE%C2%BAb-signal-transduction-as-a-tool-to-quantify-the-impact-of-drug-induced-liver-injury-compounds
#19
Angela Oppelt, Daniel Kaschek, Suzanna Huppelschoten, Rowena Sison-Young, Fang Zhang, Marie Buck-Wiese, Franziska Herrmann, Sebastian Malkusch, Carmen L Krüger, Mara Meub, Benjamin Merkt, Lea Zimmermann, Amy Schofield, Robert P Jones, Hassan Malik, Marcel Schilling, Mike Heilemann, Bob van de Water, Christopher E Goldring, B Kevin Park, Jens Timmer, Ursula Klingmüller
Drug-induced liver injury (DILI) has become a major problem for patients and for clinicians, academics and the pharmaceutical industry. To date, existing hepatotoxicity test systems are only poorly predictive and the underlying mechanisms are still unclear. One of the factors known to amplify hepatotoxicity is the tumor necrosis factor alpha (TNFα), especially due to its synergy with commonly used drugs such as diclofenac. However, the exact mechanism of how diclofenac in combination with TNFα induces liver injury remains elusive...
2018: NPJ Systems Biology and Applications
https://www.readbyqxmd.com/read/29899741/decreased-siglec-9-expression-on-natural-killer-cell-subset-associated-with-persistent-hbv-replication
#20
Di Zhao, Xuemei Jiang, Yong Xu, Huimin Yang, Dongni Gao, Xueen Li, Lifen Gao, Chunhong Ma, Xiaohong Liang
Siglec-9 is an MHC-independent inhibitory receptor selectively expressed on CD56dim NK cells. Its role in infection diseases has not been investigated yet. Here, we studied the potential regulatory roles of NK Siglec-9 in the pathogenesis of chronic hepatitis B (CHB) infection. Flow cytometry evaluated the expression of Siglec-9 and other receptors on peripheral NK cells. Immunofluorescence staining was used to detect Siglec-9 ligands on liver biopsy tissues and cultured hepatocyte cell lines. Siglec-9 blocking assay was carried out and cytokine synthesis and CD107a degranulation was detected by flow cytometry...
2018: Frontiers in Immunology
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