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https://www.readbyqxmd.com/read/28506291/targeting-cd22-with-the-monoclonal-antibody-epratuzumab-modulates-human-b-cell-maturation-and-cytokine-production-in-response-to-toll-like-receptor-7-tlr7-and-b-cell-receptor-bcr-signaling
#1
Natalia V Giltiay, Geraldine L Shu, Anthony Shock, Edward A Clark
BACKGROUND: Abnormal B-cell activation is implicated in the pathogenesis of autoimmune diseases, including systemic lupus erythematosus (SLE). The B-cell surface molecule CD22, which regulates activation through the B-cell receptor (BCR), is a potential target for inhibiting pathogenic B cells; however, the regulatory functions of CD22 remain poorly understood. In this study, we determined how targeting of CD22 with epratuzumab (Emab), a humanized anti-CD22 IgG1 monoclonal antibody, affects the activation of human B-cell subsets in response to Toll-like receptor 7 (TLR7) and BCR engagement...
May 15, 2017: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/28494239/crispr-cas9-screens-reveal-epstein-barr-virus-transformed-b-cell-host-dependency-factors
#2
Yijie Ma, Michael J Walsh, Katharina Bernhardt, Camille W Ashbaugh, Stephen J Trudeau, Isabelle Y Ashbaugh, Sizun Jiang, Chang Jiang, Bo Zhao, David E Root, John G Doench, Benjamin E Gewurz
Epstein-Barr virus (EBV) causes endemic Burkitt lymphoma (BL) and immunosuppression-related lymphomas. These B cell malignancies arise by distinct transformation pathways and have divergent viral and host expression programs. To identify host dependency factors resulting from these EBV+, B cell-transformed cell states, we performed parallel genome-wide CRISPR/Cas9 loss-of-function screens in BL and lymphoblastoid cell lines (LCLs). These highlighted 57 BL and 87 LCL genes uniquely important for their growth and survival...
May 10, 2017: Cell Host & Microbe
https://www.readbyqxmd.com/read/28442738/dysregulation-of-blimp1-transcriptional-repressor-unleashes-p130cas-erbb2-breast-cancer-invasion
#3
Marianna Sciortino, Maria Del Pilar Camacho-Leal, Francesca Orso, Elena Grassi, Andrea Costamagna, Paolo Provero, Wayne Tam, Emilia Turco, Paola Defilippi, Daniela Taverna, Sara Cabodi
ErbB2 overexpression is detected in approximately 20% of breast cancers and is correlated with poor survival. It was previously shown that the adaptor protein p130Cas/BCAR1 is a crucial mediator of ErbB2 transformation and that its overexpression confers invasive properties to ErbB2-positive human mammary epithelial cells. We herein prove, for the first time, that the transcriptional repressor Blimp1 is a novel mediator of p130Cas/ErbB2-mediated invasiveness. Indeed, high Blimp1 expression levels are detected in invasive p130Cas/ErbB2 cells and correlate with metastatic status in human breast cancer patients...
April 25, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28412245/cxcr5-cd8-t-cells-infiltrate-the-colorectal-tumors-and-nearby-lymph-nodes-and-are-associated-with-enhanced-igg-response-in-b-cells
#4
Junjie Xing, Chenxin Zhang, Xiaohong Yang, Shaoxuan Wang, Zhongchuan Wang, Xu Li, Enda Yu
Colorectal cancer is the third most prevalent cancer type worldwide and contributes to a significant percentage of cancer-related mortality. Recent studies have shown that the CXCR5(+)CD8(+) T cells present more potent proinflammatory function than CXCR5(-)CD8(+) T cells in chronic virus infections and in follicular lymphoma, but the role of CXCR5(+)CD8(+) T cells in colorectal cancer is yet unclear. In this study, we demonstrated that CXCR5(+)CD8(+) T cells were very rare in peripheral blood mononuclear cells from healthy and colorectal cancer individuals, but were significantly enriched in resected tumors and tumor-associated lymph nodes...
April 12, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28400788/the-lin28-let-7-pathway-in-cancer
#5
REVIEW
Julien Balzeau, Miriam R Menezes, Siyu Cao, John P Hagan
Among all tumor suppressor microRNAs, reduced let-7 expression occurs most frequently in cancer and typically correlates with poor prognosis. Activation of either LIN28A or LIN28B, two highly related RNA binding proteins (RBPs) and proto-oncogenes, is responsible for the global post-transcriptional downregulation of the let-7 microRNA family observed in many cancers. Specifically, LIN28A binds the terminal loop of precursor let-7 and recruits the Terminal Uridylyl Transferase (TUTase) ZCCHC11 that polyuridylates pre-let-7, thereby blocking microRNA biogenesis and tumor suppressor function...
2017: Frontiers in Genetics
https://www.readbyqxmd.com/read/28386637/2-3-7-8-tetrachlorodibenzo-p-dioxin-tcdd-mediated-deregulation-of-myeloid-and-sebaceous-gland-stem-progenitor-cell-homeostasis
#6
REVIEW
Karl Walter Bock
Studies of TCDD toxicity stimulated identification of the responsible aryl hydrocarbon receptor (AHR), a multifunctional, ligand-activated transcription factor of the basic helix-loop-helix/Per-Arnt-Sim family. Accumulating evidence suggests a role of this receptor in homeostasis of stem/progenitor cells, in addition to its known role in xenobiotic metabolism. (1) Regulation of myelopoiesis is complex. As one example, AHR-mediated downregulation of human CD34+ progenitor differentiation to monocytes/macrophages is discussed...
April 6, 2017: Archives of Toxicology
https://www.readbyqxmd.com/read/28322735/stella-collaborates-in-distinct-mesendodermal-cell-subpopulations-at-the-fetal-placental-interface-in-the-mouse-gastrula
#7
Adam D Wolfe, Adriana M Rodriguez, Karen M Downs
The allantois-derived umbilical component of the chorio-allantoic placenta shuttles fetal blood to and from the chorion, thereby ensuring fetal-maternal exchange. The progenitor populations that establish and supply the fetal-umbilical interface lie, in part, within the base of the allantois, where the germ line is claimed to segregate from the soma. Results of recent studies in the mouse have reported that STELLA (DPPA-3, PGC7) co-localizes with PRDM1 (BLIMP1), the bimolecular signature of putative primordial germ cells (PGCs) throughout the fetal-placental interface...
May 1, 2017: Developmental Biology
https://www.readbyqxmd.com/read/28314753/transethnic-meta-analysis-identifies-gsdma-and-prdm1-as-susceptibility-genes-to-systemic-sclerosis
#8
Chikashi Terao, Takahisa Kawaguchi, Philippe Dieude, John Varga, Masataka Kuwana, Marie Hudson, Yasushi Kawaguchi, Marco Matucci-Cerinic, Koichiro Ohmura, Gabriela Riemekasten, Aya Kawasaki, Paolo Airo, Tetsuya Horita, Akira Oka, Eric Hachulla, Hajime Yoshifuji, Paola Caramaschi, Nicolas Hunzelmann, Murray Baron, Tatsuya Atsumi, Paul Hassoun, Takeshi Torii, Meiko Takahashi, Yasuharu Tabara, Masakazu Shimizu, Akiko Tochimoto, Naho Ayuzawa, Hidetoshi Yanagida, Hiroshi Furukawa, Shigeto Tohma, Minoru Hasegawa, Manabu Fujimoto, Osamu Ishikawa, Toshiyuki Yamamoto, Daisuke Goto, Yoshihide Asano, Masatoshi Jinnin, Hirahito Endo, Hiroki Takahashi, Kazuhiko Takehara, Shinichi Sato, Hironobu Ihn, Soumya Raychaudhuri, Katherine Liao, Peter Gregersen, Naoyuki Tsuchiya, Valeria Riccieri, Inga Melchers, Gabriele Valentini, Anne Cauvet, Maria Martinez, Tsuneyo Mimori, Fumihiko Matsuda, Yannick Allanore
OBJECTIVES: Systemic sclerosis (SSc) is an autoimmune disease characterised by skin and systemic fibrosis culminating in organ damage. Previous genetic studies including genome-wide association studies (GWAS) have identified 12 susceptibility loci satisfying genome-wide significance. Transethnic meta-analyses have successfully expanded the list of susceptibility genes and deepened biological insights for other autoimmune diseases. METHODS: We performed transethnic meta-analysis of GWAS in the Japanese and European populations, followed by a two-staged replication study comprising a total of 4436 cases and 14 751 controls...
June 2017: Annals of the Rheumatic Diseases
https://www.readbyqxmd.com/read/28199486/gsg1-trnp1-and-tmem215-mark-subpopulations-of-bipolar-interneurons-in-the-mouse-retina
#9
Ko Uoon Park, Grace Randazzo, Kenneth L Jones, Joseph A Brzezinski
Purpose: How retinal bipolar cell interneurons are specified and assigned to specialized subtypes is only partially understood. In part, this is due to a lack of early pan- and subtype-specific bipolar cell markers. To discover these factors, we identified genes that were upregulated in Blimp1 (Prdm1) mutant retinas, which exhibit precocious bipolar cell development. Methods: Postnatal day (P)2 retinas from Blimp1 conditional knock-out (CKO) mice and controls were processed for RNA sequencing...
February 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28179525/differentiation-dependent-lmp1-expression-is-required-for-efficient-lytic-epstein-barr-virus-reactivation-in-epithelial-cells
#10
Dhananjay M Nawandar, Makoto Ohashi, Reza Djavadian, Elizabeth Barlow, Kathleen Makielski, Ahmed Ali, Denis Lee, Paul F Lambert, Eric Johannsen, Shannon C Kenney
Epstein-Barr virus (EBV)-associated diseases of epithelial cells, including tumors that have latent infection, such as nasopharyngeal carcinoma (NPC), and oral hairy leukoplakia (OHL) lesions that have lytic infection, frequently express the viral latent membrane protein 1 (LMP1). In lytically infected cells, LMP1 expression is activated by the BRLF1 (R) immediate early (IE) protein. However, the mechanisms by which LMP1 expression is normally regulated in epithelial cells remain poorly understood, and its potential roles in regulating lytic reactivation in epithelial cells are as yet unexplored...
April 15, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28150777/pathologically-expanded-peripheral-t-helper-cell-subset-drives-b-cells-in-rheumatoid-arthritis
#11
Deepak A Rao, Michael F Gurish, Jennifer L Marshall, Kamil Slowikowski, Chamith Y Fonseka, Yanyan Liu, Laura T Donlin, Lauren A Henderson, Kevin Wei, Fumitaka Mizoguchi, Nikola C Teslovich, Michael E Weinblatt, Elena M Massarotti, Jonathan S Coblyn, Simon M Helfgott, Yvonne C Lee, Derrick J Todd, Vivian P Bykerk, Susan M Goodman, Alessandra B Pernis, Lionel B Ivashkiv, Elizabeth W Karlson, Peter A Nigrovic, Andrew Filer, Christopher D Buckley, James A Lederer, Soumya Raychaudhuri, Michael B Brenner
CD4(+) T cells are central mediators of autoimmune pathology; however, defining their key effector functions in specific autoimmune diseases remains challenging. Pathogenic CD4(+) T cells within affected tissues may be identified by expression of markers of recent activation. Here we use mass cytometry to analyse activated T cells in joint tissue from patients with rheumatoid arthritis, a chronic immune-mediated arthritis that affects up to 1% of the population. This approach revealed a markedly expanded population of PD-1(hi)CXCR5(-)CD4(+) T cells in synovium of patients with rheumatoid arthritis...
February 1, 2017: Nature
https://www.readbyqxmd.com/read/28149882/simian-immunodeficiency-virus-confounds-t-follicular-helper-t-cells-and-the-germinal-centre
#12
COMMENT
Tom N Lea-Henry, Simon H Jiang
Yamamoto et al. have studied T follicular helper (TFH) and germinal centre (GC) responses after infection of rhesus macaques (RM) infected with simian immunodeficiency virus (SIV). In this study the authors examined the behaviour of TFH, reproducing infection-associated TFH accumulation and their association with the quality of antibody responses against cross-clade viral epitopes. The authors correlate TFHIL4 and CD154 expression with superior antibody responses. Accumulation of TFH was accompanied by aberrant expression of non-TFH transcriptional regulators such as BLIMP1 in TFH, suggesting viral induced abnormalities may affect TFH function...
December 2016: Annals of Translational Medicine
https://www.readbyqxmd.com/read/28097234/kruppel-like-factor4-regulates-prdm1-expression-through-binding-to-an-autoimmune-risk-allele
#13
Su Hwa Jang, Helen Chen, Peter K Gregersen, Betty Diamond, Sun Jung Kim
A SNP identified as rs548234, which is found in PRDM1, the gene that encodes BLIMP1, is a risk allele associated with systemic lupus erythematosus (SLE). BLIMP1 expression was reported to be decreased in women with the PRDM1 rs548234 risk allele compared with women with the nonrisk allele in monocyte-derived DCs (MO-DCs). In this study, we demonstrate that BLIMP1 expression is regulated by the binding of Kruppel-like factor 4 (KLF4) to the risk SNP. KLF4 is highly expressed in MO-DCs but undetectable in B cells, consistent with the lack of altered expression of BLIMP1 in B cells from risk SNP carriers...
January 12, 2017: JCI Insight
https://www.readbyqxmd.com/read/28012163/il-10-production-in-murine-igm-cd138-hi-cells-is-driven-by-blimp-1-and-downregulated-in-class-switched-cells
#14
Nao Suzuki-Yamazaki, Rieko Yanobu-Takanashi, Tadashi Okamura, Satoshi Takaki
In contrast to antibody-induced inflammatory responses, some B-cell subpopulations suppress inflammation through the production of interleukin (IL)-10. However, the mechanisms underlying Il10 gene expression during B-cell development is elusive. Here, we identify IgM(+) B220(lo) CD138(hi) cells responsible for marked IL-10 production in the bone marrow and spleen of mice. These murine IL-10-producing cells predominantly secrete IgM and have unique characteristics of long-lived plasma cells in spite of high expression of surface IgM...
December 23, 2016: European Journal of Immunology
https://www.readbyqxmd.com/read/27924626/expression-of-the-activation-markers-blimp1-foxp1-and-pstat3-in-extranodal-diffuse-large-b-cell-lymphomas
#15
Georgios Petrakis, Ioannis Kostopoulos, Ioannis Venizelos, Maria Lambropoulou, Kyriakos Vouras, Sofia Vakalopoulou, Eudokia Mandala, Constantinos Tsatalas, Nicolas Papadopoulos
Different studies have suggested that the expression of biomarkers related to lymphoid cell activation may provide information on the behavior of DLBCL. Most studies have concentrated on nodal or a mixture of nodal and extranodal lymphomas. The differential expression and potential clinical impact of these markers in a homogeneous group of extranodal DLBCLs are not well defined. In this study, we investigated the expression of three activation markers, Blimp1, Foxp1 and pStat3, in a cohort of 35 extranodal DLBCLs homogeneously treated with R-CHOP...
December 7, 2016: Histology and Histopathology
https://www.readbyqxmd.com/read/27746783/anti-lipid-igg-antibodies-are-produced-via-germinal-centers-in-a-murine-model-resembling-human-lupus
#16
Carlos Wong-Baeza, Albany Reséndiz-Mora, Luis Donis-Maturano, Isabel Wong-Baeza, Luz Zárate-Neira, Juan Carlos Yam-Puc, Juana Calderón-Amador, Yolanda Medina, Carlos Wong, Isabel Baeza, Leopoldo Flores-Romo
Anti-lipid IgG antibodies are produced in some mycobacterial infections and in certain autoimmune diseases [such as anti-phospholipid syndrome, systemic lupus erythematosus (SLE)]. However, few studies have addressed the B cell responses underlying the production of these immunoglobulins. Anti-lipid IgG antibodies are consistently found in a murine model resembling human lupus induced by chlorpromazine-stabilized non-bilayer phospholipid arrangements (NPA). NPA are transitory lipid associations found in the membranes of most cells; when NPA are stabilized they can become immunogenic and induce specific IgG antibodies, which appear to be involved in the development of the mouse model of lupus...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27734359/efficient-induction-and-isolation-of-human-primordial-germ-cell-like-cells-from-competent-human-pluripotent-stem-cells
#17
Naoko Irie, M Azim Surani
We recently reported a robust and defined culture system for the specification of human primordial germ cell-like cells (hPGCLCs) from human pluripotent stem cells (hPSCs), both embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) in vitro (Irie et al. Cell 160: 253-268, 2015). Similar attempts previously produced hPGCLCs from hPSCs at a very low efficiency, and the resulting cells were not fully characterized. A key step, which facilitated efficient hPGCLC specification from hPSCs, was the induction of a "competent" state for PGC fate via the medium containing a cocktail of four inhibitors...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27720607/the-germ-cell-fate-of-cynomolgus-monkeys-is-specified-in-the-nascent-amnion
#18
Kotaro Sasaki, Tomonori Nakamura, Ikuhiro Okamoto, Yukihiro Yabuta, Chizuru Iwatani, Hideaki Tsuchiya, Yasunari Seita, Shinichiro Nakamura, Naoto Shiraki, Tetsuya Takakuwa, Takuya Yamamoto, Mitinori Saitou
The germ cell lineage ensures reproduction and heredity. The mechanism for germ cell specification in primates, including humans, has remained unknown. In primates, upon implantation the pluripotent epiblast segregates the amnion, an extra-embryonic membrane eventually ensheathing an embryo, and thereafter initiates gastrulation to generate three germ layers. Here, we show that in cynomolgus monkeys, the SOX17/TFAP2C/BLIMP1-positive primordial germ cells (cyPGCs) originate from the dorsal amnion at embryonic day 11 (E11) prior to gastrulation...
October 24, 2016: Developmental Cell
https://www.readbyqxmd.com/read/27696611/prdm1-blimp1-is-widely-distributed-to-the-nascent-fetal-placental-interface-in-the-mouse-gastrula
#19
Maria M Mikedis, Karen M Downs
BACKGROUND: PRDM1 is a transcriptional repressor that contributes to primordial germ cell (PGC) development. During early gastrulation, epiblast-derived PRDM1 is thought to be restricted to a lineage-segregated germ line in the allantois. However, given recent findings that PGCs overlap an allantoic progenitor pool that contributes widely to the fetal-umbilical interface, posterior PRDM1 may also contribute to soma. RESULTS: Within the posterior mouse gastrula (early streak, 12-s stages, embryonic days ∼6...
January 2017: Developmental Dynamics: An Official Publication of the American Association of Anatomists
https://www.readbyqxmd.com/read/27505147/tumor-necrosis-factor-alpha-promotes-osteoclast-formation-via-pi3k-akt-pathway-mediated-blimp1-expression-upregulation
#20
LeCheng Wu, QunFeng Guo, Jun Yang, Bin Ni
Tumor necrosis factor alpha (TNF-α)-induced osteoclastogenesis have profound effects in states of inflammatory osteolysis such as rheumatoid arthritis, periprosthetic implant loosening, and periodontitis. However, the exact mechanisms by which TNF-α promotes RANKL-induced osteoclast formation remains poorly understood. B lymphocyte-induced maturation protein-1 (Blimp1) is a transcriptional repressor that plays crucial roles in the differentiation and/or function of various kinds of cells including osteoclasts...
June 2017: Journal of Cellular Biochemistry
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