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Ester Arévalo Sureda, Björn Weström, Stefan G Pierzynowski, Olena Prykhodko
BACKGROUND: The intestinal barrier is immature in newborn mammals allowing for transfer of bioactive macromolecules, e.g. protecting antibodies, from mother's milk to the blood circulation and in neonatal rodents lasts until weaning. This passage involves the neonatal-Fc-receptor (FcRn) binding IgG in the proximal and highly endocytic vacuolated enterocytes in the distal immature small intestine (SI). Recent studies have suggested an involvement of the transcription factor B-lymphocyte-induced maturation-protein-1 (Blimp-1) in the regulation of SI maturation in mice...
2016: PloS One
Ryan A Zander, Jenna J Guthmiller, Amy C Graham, Rosemary L Pope, Bradly E Burke, Daniel J J Carr, Noah S Butler
CD4 T cell-dependent antibody responses are essential for limiting Plasmodium parasite replication and the severity of malaria; however, the factors that regulate humoral immunity during highly inflammatory, Th1-biased systemic infections are poorly understood. Using genetic and biochemical approaches, we show that Plasmodium infection-induced type I interferons limit T follicular helper accumulation and constrain anti-malarial humoral immunity. Mechanistically we show that CD4 T cell-intrinsic type I interferon signaling induces T-bet and Blimp-1 expression, thereby promoting T regulatory 1 responses...
October 2016: PLoS Pathogens
Zhang Zhang, Li Liang, Dong Li, Lin Nong, Jumei Liu, Linlin Qu, Yalin Zheng, Bo Zhang, Ting Li
The loss of PRDM1 expression is common in extranodal NK/T-cell lymphoma, nasal type (EN-NK/T-NT), but the role of promoter methylation in silencing PRDM1 expression remains unclear. Hence, we performed pyrosequencing analysis to evaluate the promoter methylation of PRDM1 gene in vivo and in vitro, to analyze the association between methylation and its expression, and to assess cellular effects of PRDM1 reexpression. The promoter hypermethylation of PRDM1 gene was detected in 11 of 25 EN-NK/T-NT cases (44.0%) and NK92 and NKL cells...
October 5, 2016: Hematological Oncology
Li Jiang, Shuyu Yao, Su Huang, Jeffrey Wright, Thomas J Braciale, Jie Sun
Recent evidence has suggested that IL-10-producing effector CD8(+) T cells play an important role in regulating excessive inflammation during acute viral infections. However, the cellular and molecular cues regulating the development of IL-10-producing effector CD8(+) T cells are not completely defined. Here we show that type I interferons (IFNs) are required for the development of IL-10-producing effector CD8(+) T cells during influenza virus infection in mice. We find that type I IFNs can enhance IL-27 production by lung antigen presenting cells, thereby facilitating IL-10-producing CD8(+) T-cell development through a CD8(+) T cell non-autonomous way...
October 4, 2016: European Journal of Immunology
Xin Yao, Chengrong Li, Jun Yang, Guobing Wang, Changgang Li, Yu Xia
OBJECTIVE: This study aims to investigate the role of T follicular helper (TFH) cells in the immunopathogenesis of pediatric immune thrombocytopenia (ITP), as well as differences in TFH expansion and its regulation between newly diagnosed ITP (nITP) and chronic pediatric ITP (cITP). METHODS: Eighty-five children with ITP and 20 age-matched healthy controls were enrolled into this study. TFH cell frequencies and TFH cell-associated regulatory factors before and after treatment were analyzed by flow cytometry, RT-PCR and ELISA...
October 2016: Blood Cells, Molecules & Diseases
Angela Papale, Elena Kummer, Valentina Galbiati, Marina Marinovich, Corrado L Galli, Emanuela Corsini
Keratinocytes (KCs) play a key role in all phases of skin sensitization. We recently identified interleukin-18 (IL-18) production as useful end point for determination of contact sensitization potential of low molecular weight chemicals. The aim of this study was to identify genes involved in skin sensitizer-induced inflammasome activation and to establish their role in IL-18 production. For gene expression analysis, cells were treated for 6 h with p-phenylenediamine (PPD) as reference contact allergen; total RNA was extracted and examined with a commercially available Inflammasome Polymerase Chain Reaction (PCR) array...
September 1, 2016: Archives of Toxicology
Jason S Weinstein, Edward I Herman, Begoña Lainez, Paula Licona-Limón, Enric Esplugues, Richard Flavell, Joe Craft
Germinal center (GC) B cells undergo affinity selection, which depends on interactions with CD4(+) follicular helper T cells (TFH cells). We found that TFH cells progressed through transcriptionally and functionally distinct stages and provided differential signals for GC regulation. They initially localized proximally to mutating B cells, secreted interleukin 21 (IL-21), induced expression of the transcription factor Bcl-6 and selected high-affinity B cell clones. As the GC response evolved, TFH cells extinguished IL-21 production and switched to IL-4 production, showed robust expression of the co-stimulatory molecule CD40L, and promoted the development of antibody-secreting B cells via upregulation of the transcription factor Blimp-1...
October 2016: Nature Immunology
Y Xia, Z Y Xu-Monette, A Tzankov, X Li, G C Manyam, V Murty, G Bhagat, S Zhang, L Pasqualucci, L Zhang, C Visco, K Dybkaer, A Chiu, A Orazi, Y Zu, K L Richards, E D Hsi, W W L Choi, J H van Krieken, J Huh, M Ponzoni, A J M Ferreri, M B Møller, B M Parsons, J N Winter, M A Piris, J Westin, N Fowler, R N Miranda, C Y Ok, J Li, L J Medeiros, K H Young
PRDM1/BLIMP-1, a master regulator of plasma-cell differentiation, is frequently inactivated in activated B-cell-like (ABC) diffuse large B-cell lymphoma (DLBCL) patients. Little is known about its genetic aberrations and relevant clinical implications. We assessed a large cohort of patients with de novo DLBCL for PRDM1/BLIMP-1 deletion, mutation, and protein expression. BLIMP-1 expression was frequently associated with the ABC phenotype and plasmablastic morphologic subtype of DLBCL, yet 63% of the ABC-DLBCL patients were negative for BLIMP-1 protein expression...
August 29, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
Madori Osawa, Sohtaro Mine, Shinichiro Ota, Kengo Kato, Tsuyoshi Sekizuka, Makoto Kuroda, Michiyo Kataoka, Hitomi Fukumoto, Yuko Sato, Takayuki Kanno, Hideki Hasegawa, Keiji Ueda, Masashi Fukayama, Takuya Maeda, Soichiro Kanoh, Akihiko Kawana, Yuji Fujikura, Harutaka Katano
BACKGROUND: Primary effusion lymphoma is a rare distinct large B-cell neoplasm that is associated with Kaposi's sarcoma-associated herpesvirus (KSHV) infection. Over recent years, 9 KSHV-positive/Epstein-Barr virus (EBV)-negative PEL cell lines have been established. METHODS: Tumor cells were collected from the pleural effusion of a 49-year-old male with AIDS. Cells were grown in RPMI1640 culture medium supplemented with 10 % fetus bovine serum. Single cell cloning was performed successfully by a limiting dilution method in a 96-well plate...
2016: Infectious Agents and Cancer
Nobuko Matsushita, Midori Suzuki, Emi Ikebe, Shun Nagashima, Ryoko Inatome, Kenichi Asano, Masato Tanaka, Masayuki Matsushita, Eisaku Kondo, Hidekatsu Iha, Shigeru Yanagi
Tax1-binding protein 1 (TAX1BP1) is a ubiquitin-binding protein that restricts nuclear factor-κB (NF-κB) activation and facilitates the termination of aberrant inflammation. However, its roles in B-cell activation and differentiation are poorly understood. To evaluate the function of TAX1BP1 in B cells, we established TAX1BP1-deficient DT40 B cells that are hyper-responsive to CD40-induced extracellular signal-regulated kinase (ERK) activation signaling, exhibit prolonged and exaggerated ERK phosphorylation and show enhanced B lymphocyte-induced maturation protein 1 (Blimp-1; a transcription factor inducing plasma cell differentiation) expression that is ERK-dependent...
2016: Scientific Reports
Claudia Curci, Fabio Sallustio, Grazia Serino, Giuseppe De Palma, Mirko Trpevski, Marco Fiorentino, Michele Rossini, Marco Quaglia, Marialuisa Valente, Lucrezia Furian, Alessia Toscano, Gianna Mazzucco, Antonella Barreca, Stefania Bussolino, Loreto Gesualdo, Piero Stratta, Paolo Rigotti, Franco Citterio, Luigi Biancone, Francesco P Schena
BACKGROUND: Chronic T cell-mediated rejection (TCMR) in kidney graft is characterized by reduction of the vessel lumen with marked intimal thickening, fibrous hyperplasia of the small renal arteries and leukocyte infiltrates. The aim of this study was to find specific gene expression profiles in chronic TCMR kidney biopsies. METHODS: RNA extracted from archival formalin-fixed, paraffin-embedded renal biopsies was used for gene expression profiling. Our study included 14 patients with chronic TCMR and 10 with acute TCMR...
July 1, 2016: Nephrology, Dialysis, Transplantation
Qiaoqiao Gong, Yuejie Zhu, Pan Pang, Yuhong Huang, Junda Zhao, Jing Zhao, Xiaolin LA, Jianbing Ding
Objective To oberseve the expressions of B cell lymphoma 6 (Bcl-6) and B lymphocyte-induced maturation protein 1 (Blimp-1) in the decidua of patients with unexplained recurrent spontaneous abortion (URSA), and investigate the roles that Bcl-6 and Blimp-1 act in URSA. Methods Decidual tissues were collected from patients with URSA (URSA group) and normal pregnant women (control group). Then, we detected the expressions of Bcl-6 and Blimp-1 in the deciduas of the two groups using real-time fluorescent quantitative PCR and immunohistochemistry...
July 2016: Xi Bao Yu Fen Zi Mian Yi Xue za Zhi, Chinese Journal of Cellular and Molecular Immunology
Srijani Basu, Sheetal Kaw, Lucas D'Souza, Tushar Vaidya, Vineeta Bal, Satyajit Rath, Anna George
CD40 signaling during B cell activation is known to inhibit terminal differentiation and promote memory generation. Blimp-1 is essential for efficient plasma cell (PC) generation, and although CD40 signaling is known to inhibit Blimp-1 induction during B cell activation, the mechanisms involved have been unclear. We report that CD40 signaling induces miR-125b that targets Blimp-1 transcripts, and increases amounts of the ubiquitin ligase Hrd1 that targets BLIMP-1 protein for proteasomal degradation. CD40 signaling also inhibits the early unfolded protein response (UPR) of activated B cells that precedes the induction of terminal differentiation, and Hrd1 feeds into this pathway by targeting the core UPR component IRE-1α...
August 1, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
Moonjung Hyun, Jeongho Kim, Catherine Dumur, Frank C Schroeder, Young-Jai You
Environmental stress triggers multilevel adaptations in animal development that depend in part on epigenetic mechanisms. In response to harsh environmental conditions and pheromone signals, Caenorhabditis elegans larvae become the highly stress-resistant and long-lived dauer. Despite extensive studies of dauer formation pathways that integrate specific environmental cues and appear to depend on transcriptional reprogramming, the role of epigenetic regulation in dauer development has remained unclear. Here we report that BLMP-1, the BLIMP-1 ortholog, regulates dauer formation via epigenetic pathways; in the absence of TGF-β signaling (in daf-7 mutants), lack of blmp-1 caused lethality...
August 2016: Genetics
Y-H Yu, K-I Lin
The generation of antigen-specific neutralizing antibodies and memory B cells is one of the most important immune protections of the host and is the basis for successful vaccination strategies. The protective antibodies, secreted by preexisting long-lived plasma cells and reactivated antigen-experienced memory B cells, constitute the main humoral immune defense. Distinct from the primary antibody response, the humoral memory response is generated much faster and with greater magnitude, and it produces antibodies with higher affinity and variable isotypes...
2016: Advances in Immunology
Kazutaka Akagi, Moustafa Sarhan, Abdel-Rahman S Sultan, Haruka Nishida, Azusa Koie, Takumi Nakayama, Hitoshi Ueda
During the development of multicellular organisms, many events occur with precise timing. In Drosophila melanogaster, pupation occurs about 12 h after puparium formation and its timing is believed to be determined by the release of a steroid hormone, ecdysone (E), from the prothoracic gland. Here, we demonstrate that the ecdysone-20-monooxygenase Shade determines pupation timing by converting E to 20-hydroxyecdysone (20E) in the fat body, which is the organ that senses nutritional status. The timing of shade expression is determined by its transcriptional activator βFtz-f1...
July 1, 2016: Development
Gin-Wen Chang, Cheng-Chih Hsiao, Yen-Ming Peng, Felipe A Vieira Braga, Natasja A M Kragten, Ester B M Remmerswaal, Martijn D B van de Garde, Rachel Straussberg, Gabriele M König, Evi Kostenis, Vera Knäuper, Linde Meyaard, René A W van Lier, Klaas P J M van Gisbergen, Hsi-Hsien Lin, Jörg Hamann
Natural killer (NK) cells possess potent cytotoxic mechanisms that need to be tightly controlled. Here, we explored the regulation and function of GPR56/ADGRG1, an adhesion G protein-coupled receptor implicated in developmental processes and expressed distinctively in mature NK cells. Expression of GPR56 was triggered by Hobit (a homolog of Blimp-1 in T cells) and declined upon cell activation. Through studying NK cells from polymicrogyria patients with disease-causing mutations in ADGRG1, encoding GPR56, and NK-92 cells ectopically expressing the receptor, we found that GPR56 negatively regulates immediate effector functions, including production of inflammatory cytokines and cytolytic proteins, degranulation, and target cell killing...
May 24, 2016: Cell Reports
Ryo Shinnakasu, Takeshi Inoue, Kohei Kometani, Saya Moriyama, Yu Adachi, Manabu Nakayama, Yoshimasa Takahashi, Hidehiro Fukuyama, Takaharu Okada, Tomohiro Kurosaki
Despite the importance of memory B cells in protection from reinfection, how such memory cells are selected and generated during germinal-center (GC) reactions remains unclear. We found here that light-zone (LZ) GC B cells with B cell antigen receptors (BCRs) of lower affinity were prone to enter the memory B cell pool. Mechanistically, cells in this memory-prone fraction had higher expression of the transcriptional repressor Bach2 than that of their counterparts with BCRs of higher affinity. Haploinsufficiency of Bach2 resulted in reduced generation of memory B cells, independently of suppression of the gene encoding the transcription factor Blimp-1...
July 2016: Nature Immunology
Piers E M Patten, Gerardo Ferrer, Shih-Shih Chen, Rita Simone, Sonia Marsilio, Xiao-Jie Yan, Zachary Gitto, Chaohui Yuan, Jonathan E Kolitz, Jacqueline Barrientos, Steven L Allen, Kanti R Rai, Thomas MacCarthy, Charles C Chu, Nicholas Chiorazzi
Xenografting primary tumor cells allows modeling of the heterogeneous natures of malignant diseases and the influences of the tissue microenvironment. Here, we demonstrate that xenografting primary chronic lymphocytic leukemia (CLL) B lymphocytes with activated autologous T cells into alymphoid mice results in considerable CLL B cell division and sizable T cell expansion. Nevertheless, most/all CD5(+)CD19(+) cells are eventually lost, due in part to differentiation into antibody-secreting plasmablasts/plasma cells...
April 7, 2016: JCI Insight
Junsheng Ye, Juan Li, Minjie Zhou, Renfei Xia, Rumin Liu, Lixin Yu
BACKGROUND: Antibody-mediated rejection, mediated by donor-specific antibodies, is emerging as a leading cause for allograft dysfunction in organ transplantation. Histone deacetylase inhibitors (HDACi) have potential immunosuppressive action, but their effects on antibody-mediated rejection and B cell function in organ transplantation have not been fully explored. METHODS: The impacts of valproic acid (VPA), an HDACi, on isolated murine B cell proliferation, apoptosis, class switch recombination (CSR), differentiation, and secretion of immunoglobulin were investigated in vitro and in vivo...
May 2, 2016: Transplantation
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