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Myeloid regulatory cells

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https://www.readbyqxmd.com/read/29452230/a-regulatory-circuitry-between-mir-193a-mir-600-and-wt1-enhances-leukemogenesis-in-acute-myeloid-leukemia
#1
Haiying Li, Chongyun Xing, Bin Zhou, Haige Ye, Jianhua Feng, Jianbo Wu, Shenmeng Gao
The aberrant overexpression of the Wilm's tumor-1 (WT1) in acute myeloid leukemia (AML) plays an important role in blast cell survival through enhancing proliferation and inhibiting apoptosis. However, the mechanism underlying the overexpression of WT1 remains unclear. Here, we identified miR-193a (miR-193a-5p) and miR-600 targeting and degrading WT1. MiR-193a and miR-600 synergistically reduced WT1 expression and suppressed the activity of a luciferase reporter through binding coding sequence (CDS) and 3'-untranslated regions (3'UTR) of WT1 mRNA, respectively...
February 13, 2018: Experimental Hematology
https://www.readbyqxmd.com/read/29452207/glycogen-synthase-kinase-3%C3%AE-promotes-liver-innate-immune-activation-by-restraining-amp-activated-protein-kinase-activation
#2
Haoming Zhou, Han Wang, Ming Ni, Shi Yue, Yongxiang Xia, Ronald W Busuttil, Jerzy W Kupiec-Weglinski, Ling Lu, Xuehao Wang, Yuan Zhai
BACKGROUND & AIMS: Glycogen synthase kinase 3β (Gsk3β) is a ubiquitously expressed kinase with distinctive functions in different types of cells. Although its roles in regulating innate immune activation and ischemia and reperfusion injuries (IRI) have been well documented, underlying mechanisms remain ambiguous, due in part to the lack of cell-specific tools in vivo. METHODS: We created a myeloid-specific Gsk3β KO strain to study its function in macrophages in a murine liver partial warm ischemia model...
February 13, 2018: Journal of Hepatology
https://www.readbyqxmd.com/read/29439669/a-novel-mir-375-hoxb3-cdca3-dnmt3b-regulatory-circuitry-contributes-to-leukemogenesis-in-acute-myeloid-leukemia
#3
Laixi Bi, Bin Zhou, Haiying Li, Licai He, Chunjing Wang, Zhonggai Wang, Liqing Zhu, Mengqian Chen, Shenmeng Gao
BACKGROUND: Acute myeloid leukemia (AML) is a heterogeneous group of hematopoietic malignancies due to sophisticated genetic mutations and epigenetic dysregulation. MicroRNAs (miRNAs), a class of small non-coding RNAs, are important regulators of gene expression in all biological processes, including leukemogenesis. Recently, miR-375 has been reported to be a suppressive miRNA in multiple types of cancers, but its underlying anti-leukemia activity in AML is largely unknown. METHODS: Quantitative reverse transcriptase PCR (qRT-PCR) was used to measure the expression of miR-375 and HOXB3 in leukemic cells and normal controls...
February 13, 2018: BMC Cancer
https://www.readbyqxmd.com/read/29432481/viral-microrna-effects-on-persistent-infection-of-human-lymphoid-cells-by-polyomavirus-sv40
#4
Adrienne L McNees, Lindsay J Harrigal, Aoife Kelly, Charles G Minard, Connie Wong, Janet S Butel
BACKGROUND: Polyomaviruses, including simian virus 40 (SV40), display evidence of lymphotropic properties. This study analyzed the nature of SV40-human lymphocyte interactions in established cell lines and in primary lymphocytes. The effects of viral microRNA and the structure of the viral regulatory region on SV40 persistence were examined. RESULTS: SV40 DNA was maintained in infected B cell and myeloid cell lines during cell growth for at least 28 days. Limiting dilution analysis showed that low amounts of SV40 DNA (~2 copies per cell) were retained over time...
2018: PloS One
https://www.readbyqxmd.com/read/29431743/sorafenib-promotes-graft-versus-leukemia-activity-in-mice-and-humans-through-il-15-production-in-flt3-itd-mutant-leukemia-cells
#5
Nimitha R Mathew, Francis Baumgartner, Lukas Braun, David O'Sullivan, Simone Thomas, Miguel Waterhouse, Tony A Müller, Kathrin Hanke, Sanaz Taromi, Petya Apostolova, Anna L Illert, Wolfgang Melchinger, Sandra Duquesne, Annette Schmitt-Graeff, Lena Osswald, Kai-Li Yan, Arnim Weber, Sonia Tugues, Sabine Spath, Dietmar Pfeifer, Marie Follo, Rainer Claus, Michael Lübbert, Christoph Rummelt, Hartmut Bertz, Ralph Wäsch, Johanna Haag, Andrea Schmidts, Michael Schultheiss, Dominik Bettinger, Robert Thimme, Evelyn Ullrich, Yakup Tanriver, Giang Lam Vuong, Renate Arnold, Philipp Hemmati, Dominik Wolf, Markus Ditschkowski, Cordula Jilg, Konrad Wilhelm, Christian Leiber, Sabine Gerull, Jörg Halter, Claudia Lengerke, Thomas Pabst, Thomas Schroeder, Guido Kobbe, Wolf Rösler, Soroush Doostkam, Stephan Meckel, Kathleen Stabla, Stephan K Metzelder, Sebastian Halbach, Tilman Brummer, Zehan Hu, Joern Dengjel, Björn Hackanson, Christoph Schmid, Udo Holtick, Christof Scheid, Alexandros Spyridonidis, Friedrich Stölzel, Rainer Ordemann, Lutz P Müller, Flore Sicre-de-Fontbrune, Gabriele Ihorst, Jürgen Kuball, Jan E Ehlert, Daniel Feger, Eva-Maria Wagner, Jean-Yves Cahn, Jacqueline Schnell, Florian Kuchenbauer, Donald Bunjes, Ronjon Chakraverty, Simon Richardson, Saar Gill, Nicolaus Kröger, Francis Ayuk, Luca Vago, Fabio Ciceri, Antonia M Müller, Takeshi Kondo, Takanori Teshima, Susan Klaeger, Bernhard Kuster, Dennis Dong Hwan Kim, Daniel Weisdorf, Walter van der Velden, Daniela Dörfel, Wolfgang Bethge, Inken Hilgendorf, Andreas Hochhaus, Geoffroy Andrieux, Melanie Börries, Hauke Busch, John Magenau, Pavan Reddy, Myriam Labopin, Joseph H Antin, Andrea S Henden, Geoffrey R Hill, Glen A Kennedy, Merav Bar, Anita Sarma, Donal McLornan, Ghulam Mufti, Betul Oran, Katayoun Rezvani, Omid Sha, Robert S Negrin, Arnon Nagler, Marco Prinz, Andreas Burchert, Andreas Neubauer, Dietrich Beelen, Andreas Mackensen, Nikolas von Bubnoff, Wolfgang Herr, Burkhard Becher, Gerard Socié, Michael A Caligiuri, Eliana Ruggiero, Chiara Bonini, Georg Häcker, Justus Duyster, Jürgen Finke, Erika Pearce, Bruce R Blazar, Robert Zeiser
Individuals with acute myeloid leukemia (AML) harboring an internal tandem duplication (ITD) in the gene encoding Fms-related tyrosine kinase 3 (FLT3) who relapse after allogeneic hematopoietic cell transplantation (allo-HCT) have a 1-year survival rate below 20%. We observed that sorafenib, a multitargeted tyrosine kinase inhibitor, increased IL-15 production by FLT3-ITD+ leukemia cells. This synergized with the allogeneic CD8+ T cell response, leading to long-term survival in six mouse models of FLT3-ITD+ AML...
February 12, 2018: Nature Medicine
https://www.readbyqxmd.com/read/29427600/the-first-report-of-siglec-3-cd33-gene-in-a-teleost-rock-bream-oplegnathus-fasciatus-an-analysis-of-its-spatial-expression-during-stimulation-to-red-seabream-iridovirus-rsiv-and-two-bacterial-pathogens
#6
Joseph Jeswin, Min-Soo Joo, Ji-Min Jeong, Jin-Sol Bae, Kwang-Min Choi, Dong-Hee Cho, Son-Il Park, Chan-Il Park
Siglec-3/CD33 is a myeloid-specific inhibitory receptor that is expressed on cells of the immune system, where it is believed to play a regulatory role, modulating the inflammatory and immune responses. We characterized CD33 (RbCD33) in rock bream which is a transmembrane protein with two IG-like domains and a cytoplasmic tail. It has a deduced amino acid sequence of 390 residues and has tyrosine-based signaling motifs in the cytoplasmic tail. The RbCD33 mRNA was highly expressed in peripheral blood leukocytes and was also detected in the muscle, spleen, skin, head kidney, gills, trunk kidney, heart, stomach, brain, intestine and liver by quantitative real-time PCR...
February 7, 2018: Developmental and Comparative Immunology
https://www.readbyqxmd.com/read/29414673/evolving-targets-for-the-treatment-of-atherosclerosis
#7
REVIEW
Ankita Solanki, Lokesh Kumar Bhatt, Thomas P Johnston
Atherosclerosis is a progressive disease of large arteries and a leading cause of cardiovascular diseases and stroke. Chronic inflammation, aberrant immune response, and disturbances to key enzymes involved with lipid metabolism are characteristic features of atherosclerosis. Apart from targeting the derangements in lipid metabolism, therapeutic modulation to regulate chronic inflammation and the immune system response may prove to be very promising strategies in the management of atherosclerosis. In recent years, various targets have been studied for the treatment of atherosclerosis...
February 4, 2018: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/29413890/indoleamine-2-3-dioxygenase-and-its-therapeutic-inhibition-in-cancer
#8
George C Prendergast, William J Malachowski, Arpita Mondal, Peggy Scherle, Alexander J Muller
The tryptophan catabolic enzyme indoleamine 2,3-dioxygenase-1 (IDO1) has attracted enormous attention in driving cancer immunosuppression, neovascularization, and metastasis. IDO1 suppresses local CD8+ T effector cells and natural killer cells and induces CD4+ T regulatory cells (iTreg) and myeloid-derived suppressor cells (MDSC). The structurally distinct enzyme tryptophan dioxygenase (TDO) also has been implicated recently in immune escape and metastatic progression. Lastly, emerging evidence suggests that the IDO1-related enzyme IDO2 may support IDO1-mediated iTreg and contribute to B-cell inflammed states in certain cancers...
2018: International Review of Cell and Molecular Biology
https://www.readbyqxmd.com/read/29410647/emerging-understanding-of-the-mechanism-of-action-for-dimethyl-fumarate-in-the-treatment-of-multiple-sclerosis
#9
REVIEW
Elizabeth A Mills, Magdalena A Ogrodnik, Andrew Plave, Yang Mao-Draayer
Dimethyl fumarate (DMF) is an effective treatment option for relapsing-remitting multiple sclerosis (MS), but its therapeutic mechanism of action has not been fully elucidated. A better understanding of its mechanism will allow for the development of assays to monitor its clinical efficacy and safety in patients, as well as guide the development of the next generation of therapies for MS. In order to build the foundation for determining its mechanism, we reviewed the manner in which DMF alters lymphocyte subsets in MS patients, its impact on clinical efficacy and safety, as well as its molecular effects in cellular and animal models...
2018: Frontiers in Neurology
https://www.readbyqxmd.com/read/29408330/new-human-combined-immunodeficiency-due-to-irf4-deficiency-inherited-by-uniparental-isodisomy
#10
María Bravo García-Morato, Francisco Javier Aracil Santos, Alejandro Contreras Briones, Alfonso Blázquez Moreno, Ángela Del Pozo Maté, Ángeles Domínguez-Soto, María José Beato Merino, Lucía Del Pino Molina, Juan Torres Canizales, Ana Victoria Marin, Elena Vallespín García, Marta Feito Rodríguez, Diego Plaza López Sabando, Anaïs Jiménez-Reinoso, Yasmina Mozo Del Castillo, Francisco José Sanz Santaeufemia, Raúl de Lucas-Laguna, Paula Cárdenas, Laura Casamayor Polo, María Coronel Díaz, Mar Valés-Gómez, Ernesto Roldán Santiago, Antonio Ferreira Cerdán, Julián Nevado Blanco, Ángel L Corbí, Hugh T Reyburn, José Ramón Regueiro, Eduardo López-Granados, Rebeca Rodríguez Pena
BACKGROUND: Interferon regulatory factor 4 (IRF4) is a fundamental transcription factor in adaptive and innate immunity, due to its key role in the differentiation and functional specialization of lymphoid and myeloid lineage cells. In mouse models, IRF4 participates in bone marrow central tolerance, naïve B cell activation, germinal centre formation, plasma cell differentiation, immunoglobulin secretion, T helper subset differentiation, macrophage polarization, and dendritic cell differentiation, among other processes...
February 2, 2018: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/29408212/interaction-between-the-immune-system-and-acute-myeloid-leukemia-a-model-incorporating-promotion-of-regulatory-t-cell-expansion-by-leukemic-cells
#11
Yoshiaki Nishiyama, Yutaka Saikawa, Nobuaki Nishiyama
Population dynamics of regulatory T cells (Treg) are crucial for the underlying interplay between leukemic and immune cells in progression of acute myeloid leukemia (AML). The goal of this work is to elucidate the dynamics of a model that includes Treg, which can be qualitatively assessed by accumulating clinical findings on the impact of activated immune cell infusion after selective Treg depletion. We constructed an ordinary differential equation model to describe the dynamics of three components in AML: leukemic blast cells, mature regulatory T cells (Treg), and mature effective T cells (Teff), including cytotoxic T lymphocytes...
February 6, 2018: Bio Systems
https://www.readbyqxmd.com/read/29407585/regulatory-t-cell-inhibition-by-dasatinib-is-associated-with-natural-killer-cell-differentiation-and-a-favorable-molecular-response-the-final-results-of-the-d-first-study
#12
Yuho Najima, Chikashi Yoshida, Noriyoshi Iriyama, Shin Fujisawa, Hisashi Wakita, Shigeru Chiba, Shinichiro Okamoto, Kimihiro Kawakami, Naoki Takezako, Takashi Kumagai, Kazuma Ohyashiki, Jun Taguchi, Shingo Yano, Tadahiko Igarashi, Yasuji Kouzai, Satoshi Morita, Junichi Sakamoto, Hisashi Sakamaki, Koiti Inokuchi
We evaluated the effects of regulatory T cell (Treg) inhibition during dasatinib treatment on the anticancer immune response, particularly on natural killer (NK) cells and cytotoxic T lymphocytes (CTLs). Fifty-two newly diagnosed Japanese patients with chronic myeloid leukemia (CML) in the chronic phase were enrolled in the D-first study; all received 100 mg of dasatinib once daily and were followed for at least 36 months. The cumulative deep molecular response (DMR, MR4) rate was 65% by 36 months; the 3-year overall survival was 96%...
February 2, 2018: Leukemia Research
https://www.readbyqxmd.com/read/29407325/dexamethasone-prolongs-cardiac-allograft-survival-in-a-murine-model-through-myeloid-derived-suppressor-cells
#13
T Nakao, T Nakamura, K Masuda, T Matsuyama, H Ushigome, E Ashihara, N Yoshimura
BACKGROUND: Recently, myeloid-derived suppressor cells (MDSCs) have attracted considerable attention because of their cancer-promoting and immunosuppressive effects. The glucocorticoid dexamethasone (Dex) is an important immunosuppressive agent used to treat autoimmune diseases and organ transplant rejection. However, the mechanism by which it modulates the immune system is not completely understood. MATERIAL AND METHODS: In this study, we investigated the mechanisms by which Dex modulated the immune response in mice given an allogeneic cardiac transplant...
January 2018: Transplantation Proceedings
https://www.readbyqxmd.com/read/29401684/micrornas-as-new-biomarkers-for-diagnosis-and-prognosis-and-as-potential-therapeutic-targets-in-acute-myeloid-leukemia
#14
REVIEW
Stefania Trino, Daniela Lamorte, Antonella Caivano, Ilaria Laurenzana, Daniela Tagliaferri, Geppino Falco, Luigi Del Vecchio, Pellegrino Musto, Luciana De Luca
Acute myeloid leukemias (AML) are clonal disorders of hematopoietic progenitor cells which are characterized by relevant heterogeneity in terms of phenotypic, genotypic, and clinical features. Among the genetic aberrations that control disease development there are microRNAs (miRNAs). miRNAs are small non-coding RNAs that regulate, at post-transcriptional level, translation and stability of mRNAs. It is now established that deregulated miRNA expression is a prominent feature in AML. Functional studies have shown that miRNAs play an important role in AML pathogenesis and miRNA expression signatures are associated with chemotherapy response and clinical outcome...
February 3, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29399415/melanoma-induced-immunosuppression-is-mediated-by-hematopoietic-dysregulation
#15
Neha Kamran, Youping Li, Maria Sierra, Mahmoud S Alghamri, Padma Kadiyala, Henry D Appelman, Marta Edwards, Pedro R Lowenstein, Maria G Castro
Tumors are associated with expansion of immunosuppressive cells such as tumor associated macrophages (TAMs), regulatory T cells (Tregs) and myeloid derived suppressor cells (MDSCs). These cells promote tumor growth, angiogenesis, metastasis and immune escape. Cancer patients frequently present symptoms such as anemia, leukocytosis and/or cytopenia; associated with poor prognosis. To uncover tumor-mediated hematopoietic abnormalities and identify novel targets that can be harnessed to improve tumor-specific immune responses, we investigated the hematopoietic stem and progenitor cell compartment in melanoma bearing mice...
2018: Oncoimmunology
https://www.readbyqxmd.com/read/29396433/let-7-microrna-controls-invasion-promoting-lysosomal-changes-via-the-oncogenic-transcription-factor-myeloid-zinc-finger-1
#16
Siri Amanda Tvingsholm, Malene Bredahl Hansen, Knut Kristoffer Bundgaard Clemmensen, Ditte Marie Brix, Bo Rafn, Lisa B Frankel, Riku Louhimo, José Moreira, Sampsa Hautaniemi, Irina Gromova, Marja Jäättelä, Tuula Kallunki
Cancer cells utilize lysosomes for invasion and metastasis. Myeloid Zinc Finger1 (MZF1) is an ErbB2-responsive transcription factor that promotes invasion of breast cancer cells via upregulation of lysosomal cathepsins B and L. Here we identify let-7 microRNA, a well-known tumor suppressor in breast cancer, as a direct negative regulator of MZF1. Analysis of primary breast cancer tissues reveals a gradual upregulation of MZF1 from normal breast epithelium to invasive ductal carcinoma and a negative correlation between several let-7 family members and MZF1 mRNA, suggesting that the inverse regulatory relationship between let-7 and MZF1 may play a role in the development of invasive breast cancer...
February 3, 2018: Oncogenesis
https://www.readbyqxmd.com/read/29393979/breaking-self-tolerance-during-autoimmunity-and-cancer-immunity-myeloid-cells-and-type-i-ifn-response-regulation
#17
REVIEW
Kristin V Tarbell, Jackson G Egen
The generation and regulation of innate immune signals are key determinants of autoimmune pathogenesis. Emerging evidence suggests that parallel processes operating in the setting of solid tumors can similarly determine the balance between tolerance and immunity and ultimately the effectiveness of the antitumor immune response. In both contexts, self-specific responses start with innate immune cell activation that leads to the initial break in self-tolerance, which can be followed by immune response amplification and maturation through innate-adaptive crosstalk, and finally immune-mediated tissue/tumor destruction that can further potentiate inflammation...
February 2, 2018: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/29389020/cd71-erythroid-cells-from-neonates-born-to-women-with-preterm-labor-regulate-cytokine-and-cellular-responses
#18
Derek Miller, Roberto Romero, Ronald Unkel, Yi Xu, Felipe Vadillo-Ortega, Sonia S Hassan, Nardhy Gomez-Lopez
Neonatal CD71+ erythroid cells are thought to have immunosuppressive functions. Recently, we demonstrated that CD71+ erythroid cells from neonates born to women who underwent spontaneous preterm labor (PTL) are reduced to levels similar to those of term neonates; yet, their functional properties are unknown. Herein, we investigated the functionality of CD71+ erythroid cells from neonates born to women who underwent spontaneous preterm or term labor. CD71+ erythroid cells from neonates born to women who underwent PTL displayed a similar mRNA profile to that of those from term neonates...
February 1, 2018: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/29388481/chemotherapy-alters-the-increased-numbers-of-myeloid-derived-suppressor-and-regulatory-t-cells-in-children-with-acute-lymphoblastic-leukemia
#19
Mohamed Labib Salem, Mohamed R El-Shanshory, Said H Abdou, Mohamed S Attia, Shymaa M Sobhy, Mona F Zidan, Abdel-Aziz A Zidan
INTRODUCTION: Acute lymphoblastic leukemia (ALL) is the most common cancer diagnosed in children. The precise mechanism behind the relapse in this disease is not clearly known. One possible mechanism could be the accumulation of immunosuppressive cells, including myeloid-derived suppressor cells (MDSCs) and T regulatory cells (Tregs) which we and others have reported to mediate suppression of anti-tumor immune responses. AIM: In this study, we aimed to analyze the numbers of these cells in a population of B-ALL pediatric patients...
February 1, 2018: Immunopharmacology and Immunotoxicology
https://www.readbyqxmd.com/read/29388070/aberrant-dna-methylation-in-chronic-myeloid-leukemia-cell-fate-control-prognosis-and-therapeutic-response
#20
REVIEW
Masumeh Maleki Behzad, Saeid Shahrabi, Kaveh Jaseb, Jessika Bertacchini, Neda Ketabchi, Najmaldin Saki
Chronic myeloid leukemia (CML) is a hematopoietic stem cell malignancy characterized by the expression of the BCR-ABL1 fusion gene with different chimeric transcripts. Despite the crucial impact of constitutively active tyrosine kinase in CML pathogenesis, aberrant DNA methylation of certain genes plays an important role in disease progression and the development of drug resistance. This article reviews recent findings relevant to the effect of DNA methylation pattern of regulatory genes on various cellular activities such as cell proliferation and survival, as well as cell-signaling molecules in CML...
January 31, 2018: Biochemical Genetics
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