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Divya Singh, Himanshi Tanwar, Sudeshna Das, Lilly Ganju, Shashi Bala Singh
OBJECTIVE: Kaempferol, a natural flavonol present in various traditional medicinal plants, is known to possess potent anti-inflammatory properties. This study was designed to study the adjuvant effect of kaempferol administration along with ovalbumin antigen (K + O) in balb/c mice. METHODS: Mice were immunized with kaempferol (100 and 50 mg/kg body weight) without or with ovalbumin (20 µg/mouse). After priming, booster was administered on day 21. Antigen specific IgG titers and its subtypes, on day 28, were estimated by indirect ELISA...
February 28, 2018: Immunopharmacology and Immunotoxicology
G M Hidy
Observations of smog over the Los Angeles Basin (LAB) links high oxidant mixing ratios with poor visibility, sometimes < 5 km. By the 1970s investigators recognized that most of the aerosol affecting visibility was from gaseous oxidation products, sulfate, nitrate and organic carbon. This led to the 1972-1973 the Aerosol Characterization Experiment (ACHEX), which included observations at the ground and from aircraft. Part of ACHEX was the measurement of smog by blimp in a Lagrangian-like format. The experiment on September 6, 1973 demonstrated that a blimp could travel with the wind across the LAB, observing ozone (O3) and precursors, and particles of different size ranges...
February 12, 2018: Journal of the Air & Waste Management Association
Paulina M Budzyńska, Minna K Kyläniemi, Olli Lassila, Kalle-Pekka Nera, Jukka Alinikula
Differentiation of B cells into antibody secreting cells (ASCs), plasmablasts and plasma cells, is regulated by a network of transcription factors. Within this network factors including PAX5 and BCL6 prevent ASC differentiation and maintain the B cell phenotype. In contrast, BLIMP-1 and high IRF4 expression promote plasma cell differentiation. BLIMP-1 is thought to induce immunoglobulin secretion whereas IRF4 is needed for the survival of ASCs. The role of IRF4 in the regulation of antibody secretion has remained controversial...
February 11, 2018: Scandinavian Journal of Immunology
Khalid Muhammad, Ronald Rudolf, Duong Anh Thuy Pham, Stefan Klein-Hessling, Katsuyoshi Takata, Nobuko Matsushita, Volker Ellenrieder, Eisaku Kondo, Edgar Serfling
In lymphocytes, immune receptor signals induce the rapid nuclear translocation of preformed cytosolic NFAT proteins. Along with co-stimulatory signals, persistent immune receptor signals lead to high levels of NFATc1/αA, a short NFATc1 isoform, in effector lymphocytes. Whereas NFATc1 is not expressed in plasma cells, in germinal centers numerous centrocytic B cells express nuclear NFATc1/αA. When overexpressed in chicken DT40 B cells or murine WEHI 231 B cells, NFATc1/αA suppressed their cell death induced by B cell receptor signals and affected the expression of genes controlling the germinal center reaction and plasma cell formation...
2018: Frontiers in Immunology
Salah Elias, Elizabeth J Robertson, Elizabeth K Bikoff, Arne W Mould
The transcriptional repressor Blimp-1 originally cloned as a silencer of type I interferon (IFN)-β gene expression controls cell fate decisions in multiple tissue contexts. Conditional inactivation in the mammary gland was recently shown to disrupt epithelial cell architecture. Here we report that Blimp-1 regulates expression of viral defense, IFN signaling and MHC class I pathways, and directly targets the transcriptional activator Stat1. Blimp-1 functional loss in 3D cultures of mammary epithelial cells (MECs) results in accumulation of dsRNA and expression of type III IFN-λ...
January 10, 2018: Scientific Reports
Claire Leibler, Allan Thiolat, Carole Hénique, Chloé Samson, Caroline Pilon, Marie Tamagne, France Pirenne, Benoit Vingert, José L Cohen, Philippe Grimbert
Generation of de novo donor-specific antibodies (dnDSAs) after renal transplant is recognized as the leading cause of late transplant failure. Hence, the optimal immunosuppressive strategies to limit dnDSA development need to be defined. Recent clinical trials using the novel costimulatory blockade agent CTLA4-Ig (Belatacept) have shown that kidney transplant recipients (KTRs) treated with Belatacept have better graft survival and function and a lower proportion of dnDSAs than control-treated KTRs. Mechanisms involved in the control of humoral responses by Belatacept remain to be investigated...
January 10, 2018: Journal of the American Society of Nephrology: JASN
Muyao Guo, Madeline J Price, Dillon G Patterson, Benjamin G Barwick, Robert R Haines, Anna K Kania, John E Bradley, Troy D Randall, Jeremy M Boss, Christopher D Scharer
Epigenetic remodeling is required during B cell differentiation. However, little is known about the direct functions of epigenetic enzymes in Ab-secreting cells (ASC) in vivo. In this study, we examined ASC differentiation independent of T cell help and germinal center reactions using mice with inducible or B cell-specific deletions of Ezh2 Following stimulation with influenza virus or LPS, Ezh2-deficient ASC poorly proliferated and inappropriately maintained expression of inflammatory pathways, B cell-lineage transcription factors, and Blimp-1-repressed genes, leading to fewer and less functional ASC...
December 29, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
Dan Suan, Nike J Kräutler, Jesper L V Maag, Danyal Butt, Katherine Bourne, Jana R Hermes, Danielle T Avery, Clara Young, Aaron Statham, Michael Elliott, Marcel E Dinger, Antony Basten, Stuart G Tangye, Robert Brink
Memory B cells (MBCs) and plasma cells (PCs) constitute the two cellular outputs of germinal center (GC) responses that together facilitate long-term humoral immunity. Although expression of the transcription factor BLIMP-1 identifies cells undergoing PC differentiation, no such marker exists for cells committed to the MBC lineage. Here, we report that the chemokine receptor CCR6 uniquely marks MBC precursors in both mouse and human GCs. CCR6+ GC B cells were highly enriched within the GC light zone (LZ), were the most quiescent of all GC B cells, exhibited a cell-surface phenotype and gene expression signature indicative of an MBC transition, and possessed the augmented response characteristics of MBCs...
December 19, 2017: Immunity
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
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
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
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
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
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
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
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
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
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
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
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
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