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https://www.readbyqxmd.com/read/29209313/unconventional-pro-inflammatory-cd4-t-cell-response-in-b-cell-deficient-mice-infected-with-trypanosoma-cruzi
#1
Melisa Gorosito Serrán, Jimena Tosello Boari, Facundo Fiocca Vernengo, Cristian G Beccaría, María C Ramello, Daniela A Bermejo, Amelia G Cook, Carola G Vinuesa, Carolina L Montes, Eva V Acosta Rodriguez, Adriana Gruppi
Chagas disease, caused by the parasite Trypanosoma cruzi, is endemic in Latin America but has become a global public health concern by migration of infected people. It has been reported that parasite persistence as well as the intensity of the inflammatory immune response are determinants of the clinical manifestations of the disease. Even though inflammation is indispensable for host defense, when deregulated, it can contribute to tissue injury and organ dysfunction. Here, we report the importance of B cells in conditioning T cell response in T...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29118190/juvenile-hormone-and-20-hydroxyecdysone-coordinately-control-the-developmental-timing-of-matrix-metalloproteinase-induced-fat-body-cell-dissociation
#2
Qiangqiang Jia, Suning Liu, Di Wen, Yongxu Cheng, William G Bendena, Jian Wang, Sheng Li
Tissue remodeling is a crucial process in animal development and disease progression. Coordinately controlled by the two main insect hormones, juvenile hormone (JH) and 20-hydroxyecdysone (20E), tissues are remodeled context-specifically during insect metamorphosis. We previously discovered that two matrix metalloproteinases (Mmps) cooperatively induce fat body cell dissociation in Drosophila. However, the molecular events involved in this Mmps-mediated dissociation are unclear. Here we report that JH and 20E coordinately and precisely control the developmental timing of Mmps-induced fat body cell dissociation...
November 8, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28930664/aryl-hydrocarbon-receptor-controls-monocyte-differentiation-into-dendritic-cells-versus-macrophages
#3
Christel Goudot, Alice Coillard, Alexandra-Chloé Villani, Paul Gueguen, Adeline Cros, Siranush Sarkizova, Tsing-Lee Tang-Huau, Mylène Bohec, Sylvain Baulande, Nir Hacohen, Sebastian Amigorena, Elodie Segura
After entering tissues, monocytes differentiate into cells that share functional features with either macrophages or dendritic cells (DCs). How monocyte fate is directed toward monocyte-derived macrophages (mo-Macs) or monocyte-derived DCs (mo-DCs) and which transcription factors control these differentiation pathways remains unknown. Using an in vitro culture model yielding human mo-DCs and mo-Macs closely resembling those found in vivo in ascites, we show that IRF4 and MAFB were critical regulators of monocyte differentiation into mo-DCs and mo-Macs, respectively...
September 19, 2017: Immunity
https://www.readbyqxmd.com/read/28930660/the-irf4-gene-regulatory-module-functions-as-a-read-write-integrator-to-dynamically-coordinate-t%C3%A2-helper-cell-fate
#4
Veena Krishnamoorthy, Sunil Kannanganat, Mark Maienschein-Cline, Sarah L Cook, Jianjun Chen, Neil Bahroos, Evelyn Sievert, Emily Corse, Anita Chong, Roger Sciammas
Transcriptional regulation during CD4(+) T cell fate decisions enables their differentiation into distinct states, guiding immune responses toward antibody production via Tfh cells or inflammation by Teff cells. Tfh-Teff cell fate commitment is regulated by mutual antagonism between the transcription factors Bcl6 and Blimp-1. Here we examined how T cell receptor (TCR) signals establish and arbitrate Bcl6-Blimp-1 counter-antagonism. We found that the TCR-signal-induced transcription factor Irf4 is essential for the differentiation of Bcl6-expressing Tfh and Blimp-1-expressing Teff cells...
September 19, 2017: Immunity
https://www.readbyqxmd.com/read/28892471/dynamic-regulation-of-t-follicular-regulatory-cell-responses-by-interleukin-2-during-influenza-infection
#5
Davide Botta, Michael J Fuller, Tatiana T Marquez-Lago, Holly Bachus, John E Bradley, Amy S Weinmann, Allan J Zajac, Troy D Randall, Frances E Lund, Beatriz León, André Ballesteros-Tato
Interleukin 2 (IL-2) promotes Foxp3(+) regulatory T (Treg) cell responses, but inhibits T follicular helper (TFH) cell development. However, it is not clear how IL-2 affects T follicular regulatory (TFR) cells, a cell type with properties of both Treg and TFH cells. Using an influenza infection model, we found that high IL-2 concentrations at the peak of the infection prevented TFR cell development by a Blimp-1-dependent mechanism. However, once the immune response resolved, some Treg cells downregulated CD25, upregulated Bcl-6 and differentiated into TFR cells, which then migrated into the B cell follicles to prevent the expansion of self-reactive B cell clones...
November 2017: Nature Immunology
https://www.readbyqxmd.com/read/28886017/b-cell-phenotype-and-igd-cd27-memory-b-cells-are-affected-by-tnf-inhibitors-and-tocilizumab-treatment-in-rheumatoid-arthritis
#6
Rita A Moura, Cláudia Quaresma, Ana R Vieira, Maria J Gonçalves, Joaquim Polido-Pereira, Vasco C Romão, Nádia Martins, Helena Canhão, João E Fonseca
BACKGROUND: The use of TNF-inhibitors and/or the IL-6 receptor antagonist, tocilizumab, in rheumatoid arthritis (RA) have pleiotropic effects that also involve circulating B-cells. The main goal of this study was to assess the effect of TNF-inhibitors and tocilizumab on B-cell phenotype and gene expression in RA. METHODS: Blood samples were collected from untreated early RA (ERA) patients, established RA patients under methotrexate treatment, established RA patients before and after treatment with TNF-inhibitors and tocilizumab, and healthy donors...
2017: PloS One
https://www.readbyqxmd.com/read/28842558/hsp70-hrd1-axis-precludes-the-oncorepressor-potential-of-n-terminal-misfolded-blimp-1s-in-lymphoma-cells
#7
Wen-Fang Wang, Li Yan, Zhao Liu, Lan-Xuan Liu, Jian Lin, Zhi-Yin Liu, Xiong-Ping Chen, Wu Zhang, Zi-Zhen Xu, Ting Shi, Jun-Min Li, Yi-Lei Zhao, Guoyu Meng, Yi Xia, Jian-Yong Li, Jiang Zhu
B lymphocyte-induced maturation protein-1 (Blimp-1) ensures B-cell differentiation into the plasma cell stage, and its instability constitutes a crucial oncogenic element in certain aggressive cases of activated B cell-like diffuse large B-cell lymphoma (ABC-DLBCL). However, the underlying degradation mechanisms and their possible therapeutic relevance remain unexplored. Here, we show that N-terminal misfolding mutations in ABC-DLBCL render Blimp-1 protein susceptible to proteasome-mediated degradation but spare its transcription-regulating activity...
August 25, 2017: Nature Communications
https://www.readbyqxmd.com/read/28835458/il-2-shapes-the-survival-and-plasticity-of-il-17-producing-%C3%AE-%C3%AE-t-cells
#8
Theresa M Corpuz, Rodrigo Vazquez-Lombardi, Jason K Luong, Joanna Warren, Jessica Stolp, Daniel Christ, Cecile King, Robert Brink, Jonathan Sprent, Kylie E Webster
IL-17-producing γδ T (γδT-17) cells have proved to be an important early source of IL-17 in many inflammatory settings and are emerging as an important participant in protumor immune responses. Considering that their peripheral activation depends largely on innate signals rather than TCR ligation, it is important to understand what mechanisms exist to curb unwanted activation. Expression of the high-affinity IL-2R on γδT-17 cells prompted us to investigate a role for this cytokine. We found γδT-17 cells to be enriched, not depleted, in IL-2-deficient mice...
October 1, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28827827/transient-expression-of-zbtb32-in-anti-viral-cd8-t-cells-limits-the-magnitude-of-the-effector-response-and-the-generation-of-memory
#9
Hyun Mu Shin, Varun N Kapoor, Gwanghun Kim, Peng Li, Hang-Rae Kim, M Suresh, Susan M Kaech, E John Wherry, Liisa K Selin, Warren J Leonard, Raymond M Welsh, Leslie J Berg
Virus infections induce CD8+ T cell responses comprised of a large population of terminal effector cells and a smaller subset of long-lived memory cells. The transcription factors regulating the relative expansion versus the long-term survival potential of anti-viral CD8+ T cells are not completely understood. We identified ZBTB32 as a transcription factor that is transiently expressed in effector CD8+ T cells. After acute virus infection, CD8+ T cells deficient in ZBTB32 showed enhanced virus-specific CD8+ T cell responses, and generated increased numbers of virus-specific memory cells; in contrast, persistent expression of ZBTB32 suppressed memory cell formation...
August 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28790065/gsk3-inhibition-drives-maturation-of-nk-cells-and-enhances-their-antitumor-activity
#10
Frank Cichocki, Bahram Valamehr, Ryan Bjordahl, Bin Zhang, Betsy Rezner, Paul Rogers, Svetlana Gaidarova, Stacey Moreno, Katie Tuininga, Phillip Dougherty, Valarie McCullar, Peter Howard, Dhifaf Sarhan, Emily Taras, Heinrich Schlums, Stewart Abbot, Daniel Shoemaker, Yenan T Bryceson, Bruce R Blazar, Scott Wolchko, Sarah Cooley, Jeffrey S Miller
Maturation of human natural killer (NK) cells as defined by accumulation of cell-surface expression of CD57 is associated with increased cytotoxic character and TNF and IFNγ production upon target-cell recognition. Notably, multiple studies point to a unique role for CD57(+) NK cells in cancer immunosurveillance, yet there is scant information about how they mature. In this study, we show that pharmacologic inhibition of GSK3 kinase in peripheral blood NK cells expanded ex vivo with IL15 greatly enhances CD57 upregulation and late-stage maturation...
October 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/28783670/low-cd21-expression-defines-a-population-of-recent-germinal-center-graduates-primed-for-plasma-cell-differentiation
#11
Denise Lau, Linda Yu-Ling Lan, Sarah F Andrews, Carole Henry, Karla Thatcher Rojas, Karlynn E Neu, Min Huang, Yunping Huang, Brandon DeKosky, Anna-Karin E Palm, Gregory C Ippolito, George Georgiou, Patrick C Wilson
In this study, we report that antigen-specific CD19(+)CD27(+)CD21(lo) (CD21(lo)) B cells are transiently induced 14 to 28 days after immunization, at the time germinal centers (GCs) peak. Although clonally related to memory B cells and plasmablasts, CD21(lo) cells form distinct clades within phylogenetic trees based on accumulated variable gene mutations, supporting exit from active GCs. CD21(lo) cells express a transcriptional program, suggesting that they are primed for plasma cell differentiation and are refractory to GC differentiation, although they do not spontaneously secrete antibody...
January 27, 2017: Science Immunology
https://www.readbyqxmd.com/read/28771465/ebv-epigenetically-suppresses-the-b-cell-to-plasma-cell-differentiation-pathway-while-establishing-long-term-latency
#12
Christine T Styles, Quentin Bazot, Gillian A Parker, Robert E White, Kostas Paschos, Martin J Allday
Mature human B cells infected by Epstein-Barr virus (EBV) become activated, grow, and proliferate. If the cells are infected ex vivo, they are transformed into continuously proliferating lymphoblastoid cell lines (LCLs) that carry EBV DNA as extra-chromosomal episomes, express 9 latency-associated EBV proteins, and phenotypically resemble antigen-activated B-blasts. In vivo similar B-blasts can differentiate to become memory B cells (MBC), in which EBV persistence is established. Three related latency-associated viral proteins EBNA3A, EBNA3B, and EBNA3C are transcription factors that regulate a multitude of cellular genes...
August 2017: PLoS Biology
https://www.readbyqxmd.com/read/28751776/hobit-expression-by-a-subset-of-human-liver-resident-cd56-bright-natural-killer-cells
#13
Sebastian Lunemann, Gloria Martrus, Hanna Goebels, Tobias Kautz, Annika Langeneckert, Wilhelm Salzberger, Martina Koch, Madeleine J Bunders, Björn Nashan, Klaas P J M van Gisbergen, Marcus Altfeld
Immune responses show a high degree of tissue specificity shaped by factors influencing tissue egress and retention of immune cells. The transcription factor Hobit was recently shown to regulate tissue-residency in mice. Whether Hobit acts in a similar capacity in humans remains unknown. Our aim was to assess the expression and contribution of Hobit to tissue-residency of Natural Killer (NK) cells in the human liver. The human liver was enriched for CD56(bright) NK cells showing increased expression levels of the transcription factor Hobit...
July 27, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28738016/eomesodermin-promotes-the-development-of-type-1-regulatory-t-tr1-cells
#14
Ping Zhang, Jason S Lee, Kate H Gartlan, Iona S Schuster, Iain Comerford, Antiopi Varelias, Md Ashik Ullah, Slavica Vuckovic, Motoko Koyama, Rachel D Kuns, Kelly R Locke, Kirrilee J Beckett, Stuart D Olver, Luke D Samson, Marcela Montes de Oca, Fabian de Labastida Rivera, Andrew D Clouston, Gabrielle T Belz, Bruce R Blazar, Kelli P MacDonald, Shaun R McColl, Ranjeny Thomas, Christian R Engwerda, Mariapia A Degli-Esposti, Axel Kallies, Siok-Keen Tey, Geoffrey R Hill
Type 1 regulatory T (TR1) cells are Foxp3(-) interleukin-10 (IL-10)-producing CD4(+) T cells with potent immunosuppressive properties, but their requirements for lineage development have remained elusive. We show that TR1 cells constitute the most abundant regulatory population after allogeneic bone marrow transplantation (BMT), express the transcription factor Eomesodermin (Eomes), and are critical for the prevention of graft-versus-host disease. We demonstrate that Eomes is required for TR1 cell differentiation, during which it acts in concert with the transcription factor B lymphocyte-induced maturation protein-1 (Blimp-1) by transcriptionally activating IL-10 expression and repressing differentiation into other T helper cell lineages...
April 7, 2017: Science Immunology
https://www.readbyqxmd.com/read/28732506/new-insights-into-blimp-1-in-t-lymphocytes-a-divergent-regulator-of-cell-destiny-and-effector-function
#15
REVIEW
Shin-Huei Fu, Li-Tzu Yeh, Chin-Chen Chu, B Lin-Ju Yen, Huey-Kang Sytwu
B lymphocyte-induced maturation protein-1 (Blimp-1) serves as a master regulator of the development and function of antibody-producing B cells. Given that its function in T lymphocytes has been identified within the past decade, we review recent findings with emphasis on its role in coordinated control of gene expression during the development, differentiation, and function of T cells. Expression of Blimp-1 is mainly confined to activated T cells and is essential for the production of interleukin (IL)-10 by a subset of forkhead box (Fox)p3(+) regulatory T cells with an effector phenotype...
July 21, 2017: Journal of Biomedical Science
https://www.readbyqxmd.com/read/28713870/il-10-induces-a-stat3-dependent-autoregulatory-loop-in-th2-cells-that-promotes-blimp-1-restriction-of-cell-expansion-via-antagonism-of-stat5-target-genes
#16
Amanda C Poholek, Dragana Jankovic, Alejandro V Villarino, Franziska Petermann, Angela Hettinga, Dror S Shouval, Scott B Snapper, Susan M Kaech, Stephen R Brooks, Golnaz Vahedi, Alan Sher, Yuka Kanno, John J O'Shea
Blimp-1 expression in T cells extinguishes the fate of T follicular helper cells, drives terminal differentiation, and limits autoimmunity. Although various factors have been described to control Blimp-1 expression in T cells, little is known about what regulates Blimp-1 expression in T helper 2 (TH2) cells and the molecular basis of its actions. We report that signal transducer and activator of transcription 3 (STAT3) unexpectedly played a critical role in regulating Blimp-1 in TH2 cells. Furthermore, we found that the cytokine interleukin-10 (IL-10) acted directly on TH2 cells and was necessary and sufficient to induce optimal Blimp-1 expression through STAT3...
October 2016: Science Immunology
https://www.readbyqxmd.com/read/28698287/blimp-1-dependent-and-independent-natural-antibody-production-by-b-1-and-b-1-derived-plasma-cells
#17
Hannah P Savage, Vanessa M Yenson, Sanjam S Sawhney, Betty J Mousseau, Frances E Lund, Nicole Baumgarth
Natural antibodies contribute to tissue homeostasis and protect against infections. They are secreted constitutively without external antigenic stimulation. The differentiation state and regulatory pathways that enable continuous natural antibody production by B-1 cells, the main cellular source in mice, remain incompletely understood. Here we demonstrate that natural IgM-secreting B-1 cells in the spleen and bone marrow are heterogeneous, consisting of (a) terminally differentiated B-1-derived plasma cells expressing the transcriptional regulator of differentiation, Blimp-1, (b) Blimp-1(+), and (c) Blimp-1(neg) phenotypic B-1 cells...
September 4, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28692065/increased-cathepsin-s-in-prdm1-dendritic-cells-alters-the-tfh-cell-repertoire-and-contributes-to-lupus
#18
Sun Jung Kim, Sebastian Schätzle, S Sohail Ahmed, Wolfgang Haap, Su Hwa Jang, Peter K Gregersen, George Georgiou, Betty Diamond
Aberrant population expansion of follicular helper T cells (TFH cells) occurs in patients with lupus. An unanswered question is whether an altered repertoire of T cell antigen receptors (TCRs) is associated with such expansion. Here we found that the transcription factor Blimp-1 (encoded by Prdm1) repressed expression of the gene encoding cathepsin S (Ctss), a cysteine protease that cleaves invariant chains and produces antigenic peptides for loading onto major histocompatibility complex (MHC) class II molecules...
September 2017: Nature Immunology
https://www.readbyqxmd.com/read/28677680/ctcf-orchestrates-the-germinal-centre-transcriptional-program-and-prevents-premature-plasma-cell-differentiation
#19
Arantxa Pérez-García, Ester Marina-Zárate, Ángel F Álvarez-Prado, Jose M Ligos, Niels Galjart, Almudena R Ramiro
In germinal centres (GC) mature B cells undergo intense proliferation and immunoglobulin gene modification before they differentiate into memory B cells or long-lived plasma cells (PC). GC B-cell-to-PC transition involves a major transcriptional switch that promotes a halt in cell proliferation and the production of secreted immunoglobulins. Here we show that the CCCTC-binding factor (CTCF) is required for the GC reaction in vivo, whereas in vitro the requirement for CTCF is not universal and instead depends on the pathways used for B-cell activation...
July 5, 2017: Nature Communications
https://www.readbyqxmd.com/read/28664185/the-mir-125a-and-mir-320c-are-potential-tumor-suppressor-micrornas-epigenetically-silenced-by-the-polycomb-repressive-complex-2-in-multiple-myeloma
#20
Mohammad Alzrigat, Helena Jernberg-Wiklund
We have previously presented the histone methyltransferase enhancer of zeste homolog 2 (EZH2) of the polycomb repressive complex 2 (PRC2) as a potential therapeutic target in Multiple Myeloma (MM). In a recent article in Oncotarget by Alzrigat. et al. 2017, we have reported on the novel finding that EZH2 inhibition using the highly selective inhibitor of EZH2 enzymatic activity, UNC1999, reactivated the expression of microRNA genes previously reported to be underexpressed in MM. Among these, we have identified miR-125a-3p and miR-320c as potential tumor suppressor microRNAs as they were predicted to target MM-associated oncogenes; IRF-4, XBP-1 and BLIMP-1...
2017: RNA & Disease
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