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https://www.readbyqxmd.com/read/29686676/interleukin-10-producing-dc-10-is-a-unique-tool-to-promote-tolerance-via-antigen-specific-t-regulatory-type-1-cells
#1
REVIEW
Michela Comi, Giada Amodio, Silvia Gregori
The prominent role of tolerogenic dendritic cells (tolDCs) in promoting immune tolerance and the development of efficient methods to generate clinical grade products allow the application of tolDCs as cell-based approach to dampen antigen (Ag)-specific T cell responses in autoimmunity and transplantation. Interleukin (IL)-10 potently modulates the differentiation and functions of myeloid cells. Our group contributed to the identification of IL-10 as key factor in inducing a subset of human tolDCs, named dendritic cell (DC)-10, endowed with the ability to spontaneously release IL-10 and induce Ag-specific T regulatory type 1 (Tr1) cells...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29674674/the-e3-ubiquitin-ligase-pellino2-mediates-priming-of-the-nlrp3-inflammasome
#2
Fiachra Humphries, Ronan Bergin, Ruaidhri Jackson, Nezira Delagic, Bingwei Wang, Shuo Yang, Alice V Dubois, Rebecca J Ingram, Paul N Moynagh
The NLRP3 inflammasome has an important function in inflammation by promoting the processing of pro-IL-1β and pro-IL-18 to their mature bioactive forms, and by inducing cell death via pyroptosis. Here we show a critical function of the E3 ubiquitin ligase Pellino2 in facilitating activation of the NLRP3 inflammasome. Pellino2-deficient mice and myeloid cells have impaired activation of NLRP3 in response to toll-like receptor priming, NLRP3 stimuli and bacterial challenge. These functions of Pellino2 in the NLRP3 pathway are dependent on Pellino2 FHA and RING-like domains, with Pellino2 promoting the ubiquitination of NLRP3 during the priming phase of activation...
April 19, 2018: Nature Communications
https://www.readbyqxmd.com/read/29670037/expression-and-regulation-of-thymic-stromal-lymphopoietin-and-thymic-stromal-lymphopoietin-receptor-heterocomplex-in-the-innate-adaptive-immunity-of-pediatric-asthma
#3
REVIEW
Sheng-Chieh Lin, Fang-Yi Cheng, Jun-Jen Liu, Yi-Ling Ye
Asthma is a chronic inflammatory disease affecting the airway, and it is characterized by a wheezing breathing sound, variable airflow obstruction and the presence of inflammatory cells in the submucosa of the bronchi. Viral infection, pollutants and sensitivity to aeroallergens damage the epithelium from childhood, which causes asthma. The pathogenesis of asthma includes pathways of innate stimulation by environmental microbes and irritant pathogens. Damaged epithelial cells produce thymic stromal lymphopoietin (TSLP) and stimulate myeloid dendritic cell maturation through the thymic stromal lymphopoietin receptor (TSLPR) heterocomplex...
April 18, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29669721/ppar-%C3%AE-contributes-to-immunity-by-cancer-vaccines-that-secrete-gm-csf
#4
Girija Goyal, Karrie Wong, Christopher J Nirschl, Nicholas Souders, Donna Neuberg, Niroshana Anandasabapathy, Glenn Dranoff
Peroxisome proliferator activated receptor-γ (PPARγ) is a lipid-activated nuclear receptor that promotes immune tolerance through effects on macrophages, dendritic cells (DCs), and regulatory T cells (Tregs). Granulocyte-macrophage colony stimulating factor (GM-CSF) induces PPARγ expression in multiple myeloid cell types. GM-CSF contributes to both immune tolerance and protection, but the role of PPARγ in these pathways is poorly understood. Here we reveal an unexpected stimulatory role for PPARγ in the generation of antitumor immunity with irradiated, GM-CSF-secreting tumor-cell vaccines (GVAX)...
April 18, 2018: Cancer Immunology Research
https://www.readbyqxmd.com/read/29666124/generation-of-a-double-binary-transgenic-zebrafish-model-to-study-myeloid-gene-regulation-in-response-to-oncogene-activation-in-melanocytes
#5
Amy Kenyon, Daria Gavriouchkina, Jernej Zorman, Vanessa Chong-Morrison, Giorgio Napolitani, Vincenzo Cerundolo, Tatjana Sauka-Spengler
A complex network of inflammatory genes is closely linked to somatic cell transformation and malignant disease. Immune cells and their associated molecules are responsible for detecting and eliminating cancer cells as they establish themselves as the precursors of a tumour. By the time a patient has a detectable solid tumour, cancer cells have escaped the initial immune response mechanisms. Here, we describe the development of a double binary zebrafish model that enables regulatory programming of the myeloid cells as they respond to oncogene-activated melanocytes to be explored, focussing on the initial phase when cells become the precursors of cancer...
April 6, 2018: Disease Models & Mechanisms
https://www.readbyqxmd.com/read/29665865/integrative-analysis-reveals-functional-and-regulatory-roles-of-h3k79me2-in-mediating-alternative-splicing
#6
Tianbao Li, Qi Liu, Nick Garza, Steven Kornblau, Victor X Jin
BACKGROUND: Accumulating evidence suggests alternative splicing (AS) is a co-transcriptional splicing process not only controlled by RNA-binding splicing factors, but also mediated by epigenetic regulators, such as chromatin structure, nucleosome density, and histone modification. Aberrant AS plays an important role in regulating various diseases, including cancers. METHODS: In this study, we integrated AS events derived from RNA-seq with H3K79me2 ChIP-seq data across 34 different normal and cancer cell types and found the higher enrichment of H3K79me2 in two AS types, skipping exon (SE) and alternative 3' splice site (A3SS)...
April 17, 2018: Genome Medicine
https://www.readbyqxmd.com/read/29657293/mir-146-and-mir-155-two-key-modulators-of-immune-response-and-tumor-development
#7
REVIEW
Ugo Testa, Elvira Pelosi, Germana Castelli, Catherine Labbaye
MicroRNAs (miRNAs or miRs) are a class of evolutionarily-conserved small, regulatory non-coding RNAs, 19-3 nucleotides in length, that negatively regulate protein coding gene transcripts' expression. miR-146 (146a and 146b) and miR-155 are among the first and most studied miRs for their multiple roles in the control of the innate and adaptive immune processes and for their deregulation and oncogenic role in some tumors. In the present review, we have focused on the recent acquisitions about the key role played by miR-146a, miR-146b and miR-155 in the control of the immune system and in myeloid tumorigenesis...
June 26, 2017: Non-Coding RNA
https://www.readbyqxmd.com/read/29650945/impact-of-regulatory-t-cells-on-innate-immune-cells-in-a-pre-sensitized-heart-transplant-model
#8
Weihua Gong, Baoqing Liu, Juntao Chen, Chen Liu, Zhonghua Shen
BACKGROUND Although our previous studies revealed the role of Tregs (regulatory T cells) and MDSCs (myeloid-derived suppressor cells) in a pre-sensitized cardiac transplant model, interplay between Tregs and NK cells, neutrophils, and macrophages remain undefined. MATERIAL AND METHODS Mice heart transplantation with skin pre-sensitization was performed, in which prolonged-cold ischemia time (PCI) was used for donor treatment. Syngeneic heterotopic heart transplant recipients with PCI were treated with PC61 (monoclonal anti-CD25 antibodies), adoptive cell transfer with Tregs, and rapamycin...
April 13, 2018: Annals of Transplantation: Quarterly of the Polish Transplantation Society
https://www.readbyqxmd.com/read/29622796/nf%C3%AE%C2%BAb-regulates-p21-expression-and-controls-dna-damage-induced-leukemic-differentiation
#9
Claudia M Nicolae, Michael J O'Connor, Daniel Constantin, George-Lucian Moldovan
DNA damage exposure is a major modifier of cell fate in both normal and cancer tissues. In response to DNA damage, myeloid leukemia cells activate a poorly understood terminal differentiation process. Here, we show that the NFκB pathway directly activates expression of the proliferation inhibitor p21 in response to DNA damage in myeloid leukemia cells. In order to understand the role of this unexpected regulatory event, we ablated the NFκB binding site we identified in the p21 promoter, using CRISPR/Cas9-mediated genome editing...
April 6, 2018: Oncogene
https://www.readbyqxmd.com/read/29621426/tumor-infiltrating-treg-mdsc-and-ido-expression-associated-with-outcomes-of-neoadjuvant-chemotherapy-of-breast-cancer
#10
Fangxuan Li, Yang Zhao, Lijuan Wei, Shixia Li, Juntian Liu
BACKGROUND: Regulatory T cells(Tregs) and myeloid-derived suppressor cells(MDSCs) represent two immunosuppressive cell populations that are important in the establishment and maintenance of cancer immune tolerance. MDSCs can express IDO and promote immune tolerance via expansion of Treg cell. METHOD: We use needle biopsy breast cancer tissues prior to neoadjuvant chemotherapy(NCT) staining for CD33, Foxp3 and IDO by immunohistochemistry to evaluate whether they were correlated with subsequent treatment responses in breast cancer...
April 5, 2018: Cancer Biology & Therapy
https://www.readbyqxmd.com/read/29620143/exploring-the-molecular-mechanisms-of-osteosarcoma-by-the-integrated-analysis-of-mrnas-and-mirna-microarrays
#11
Hao Shen, Wei Wang, Bingbing Ni, Qiang Zou, Hua Lu, Zhanchao Wang
Osteosarcoma (OS) is the most frequently occurring primary bone malignancy with a rapid progression and poor survival. In the present study, in order to examine the molecular mechanisms of OS, we analyzed the microarray of GSE28425. GSE28425 was downloaded from Gene Expression Omnibus, which also included the miRNA expression profile, GSE28423, and the mRNA expression profile, GSE28424. Each of the expression profiles included 19 OS cell lines and 4 normal bones. The differentially expressed genes (DEGs) and differentially expressed miRNAs (DE-miRNAs) were screened using the limma package in Bioconductor...
March 27, 2018: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29618496/cell-centred-meta-analysis-reveals-baseline-predictors-of-anti-tnf%C3%AE-non-response-in-biopsy-and-blood-of-patients-with-ibd
#12
Renaud Gaujoux, Elina Starosvetsky, Naama Maimon, Francesco Vallania, Haggai Bar-Yoseph, Sigal Pressman, Roni Weisshof, Idan Goren, Keren Rabinowitz, Matti Waterman, Henit Yanai, Iris Dotan, Edmond Sabo, Yehuda Chowers, Purvesh Khatri, Shai S Shen-Orr
OBJECTIVE: Although anti-tumour necrosis factor alpha (anti-TNFα) therapies represent a major breakthrough in IBD therapy, their cost-benefit ratio is hampered by an overall 30% non-response rate, adverse side effects and high costs. Thus, finding predictive biomarkers of non-response prior to commencing anti-TNFα therapy is of high value. DESIGN: We analysed publicly available whole-genome expression profiles of colon biopsies obtained from multiple cohorts of patients with IBD using a combined computational deconvolution-meta-analysis paradigm which allows to estimate immune cell contribution to the measured expression and capture differential regulatory programmes otherwise masked due to variation in cellular composition...
April 4, 2018: Gut
https://www.readbyqxmd.com/read/29617660/genomic-pathway-network-and-immunologic-features-distinguishing-squamous-carcinomas
#13
Joshua D Campbell, Christina Yau, Reanne Bowlby, Yuexin Liu, Kevin Brennan, Huihui Fan, Alison M Taylor, Chen Wang, Vonn Walter, Rehan Akbani, Lauren Averett Byers, Chad J Creighton, Cristian Coarfa, Juliann Shih, Andrew D Cherniack, Olivier Gevaert, Marcos Prunello, Hui Shen, Pavana Anur, Jianhong Chen, Hui Cheng, D Neil Hayes, Susan Bullman, Chandra Sekhar Pedamallu, Akinyemi I Ojesina, Sara Sadeghi, Karen L Mungall, A Gordon Robertson, Christopher Benz, Andre Schultz, Rupa S Kanchi, Carl M Gay, Apurva Hegde, Lixia Diao, Jing Wang, Wencai Ma, Pavel Sumazin, Hua-Sheng Chiu, Ting-Wen Chen, Preethi Gunaratne, Larry Donehower, Janet S Rader, Rosemary Zuna, Hikmat Al-Ahmadie, Alexander J Lazar, Elsa R Flores, Kenneth Y Tsai, Jane H Zhou, Anil K Rustgi, Esther Drill, Ronglei Shen, Christopher K Wong, Joshua M Stuart, Peter W Laird, Katherine A Hoadley, John N Weinstein, Myron Peto, Curtis R Pickering, Zhong Chen, Carter Van Waes
This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smoking and/or human papillomavirus (HPV). SCCs harbor 3q, 5p, and other recurrent chromosomal copy-number alterations (CNAs), DNA mutations, and/or aberrant methylation of genes and microRNAs, which are correlated with the expression of multi-gene programs linked to squamous cell stemness, epithelial-to-mesenchymal differentiation, growth, genomic integrity, oxidative damage, death, and inflammation...
April 3, 2018: Cell Reports
https://www.readbyqxmd.com/read/29610256/myeloid-differentiation-factor-88-myd88-and-il-1r1-signaling-contribute-to-resistance-to-coccidioides-immitis
#14
Suganya Viriyakosol, Lorraine Walls, Sharon Okamoto, Eyal Raz, David L Williams, Joshua Fierer
Rodents are a natural host for the dimorphic pathogenic fungi Coccidioides immitis and posadasii , and mice are a good model for human infection. Humans and rodents both express Dectin-1 and TLR2 on myeloid cells and those receptors collaborate to maximize the cytokine/chemokine responses to spherules (the tissue form of the fungi), and to formalin killed spherules (FKS). We showed that Dectin-1 is necessary for resistance to pulmonary coccidioidomycosis, but the importance of TLR2 in vivo is uncertain. MyD88 is the adapter protein for TLR2 and 4, and IL-1R1 and IL-18R1...
April 2, 2018: Infection and Immunity
https://www.readbyqxmd.com/read/29610029/final-3-year-results-of-the-dasatinib-discontinuation-trial-in-patients-with-chronic-myeloid-leukemia-who-received-dasatinib-as-a-second-line-treatment
#15
Masaya Okada, Jun Imagawa, Hideo Tanaka, Hirohisa Nakamae, Masayuki Hino, Kazunori Murai, Yoji Ishida, Takashi Kumagai, Seiichi Sato, Kazuteru Ohashi, Hisashi Sakamaki, Hisashi Wakita, Nobuhiko Uoshima, Yasunori Nakagawa, Yosuke Minami, Masahiro Ogasawara, Tomoharu Takeoka, Hiroshi Akasaka, Takahiko Utsumi, Naokuni Uike, Tsutomu Sato, Sachiko Ando, Kensuke Usuki, Syuichi Mizuta, Satoshi Hashino, Tetsuhiko Nomura, Masato Shikami, Hisashi Fukutani, Yokiko Ohe, Hiroshi Kosugi, Hirohiko Shibayama, Yasuhiro Maeda, Toshihiro Fukushima, Hirohito Yamazaki, Kazuo Tsubaki, Toshimasa Kukita, Yoko Adachi, Toshiki Nataduka, Hiroto Sakoda, Hisayuki Yokoyama, Takahiro Okamoto, Yukari Shirasugi, Yasushi Onishi, Masaharu Nohgawa, Satoshi Yoshihara, Satoshi Morita, Junichi Sakamoto, Shinya Kimura
INTRODUCTION: We previously reported an interim analysis of the DADI (dasatinib discontinuation) trial. The results showed that 48% of patients with chronic myeloid leukemia in the chronic phase who maintained a deep molecular response (DMR) for ≥ 1 year could discontinue second- or subsequent-line dasatinib treatment safely at a median follow-up of 20 months. However, the results from longer follow-up periods would be much more useful from a clinical perspective. PATIENTS AND METHODS: The DADI trial was a prospective, multicenter trial conducted in Japan...
March 15, 2018: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/29601534/heterogeneity-in-immune-cell-content-in-malignant-pleural-mesothelioma
#16
REVIEW
Jorien Minnema-Luiting, Heleen Vroman, Joachim Aerts, Robin Cornelissen
Malignant pleural mesothelioma (MPM) is a highly aggressive cancer with limited therapy options and dismal prognosis. In recent years, the role of immune cells within the tumor microenvironment (TME) has become a major area of interest. In this review, we discuss the current knowledge of heterogeneity in immune cell content and checkpoint expression in MPM in relation to prognosis and prediction of treatment efficacy. Generally, immune-suppressive cells such as M2 macrophages, myeloid-derived suppressor cells and regulatory T cells are present within the TME, with extensive heterogeneity in cell numbers...
March 30, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29599138/telomerase-mediates-lymphocyte-proliferation-but-not-the-atherosclerosis-suppressive-potential-of-regulatory-t-cells
#17
Gavin Richardson, Andrew Sage, Karim Bennaceur, Nayef Al Zhrany, Jose Coelho-Lima, Emily Dookun, Lilia Draganova, Gabriele Saretzki, David T Breault, Ziad Mallat, Ioakim Spyridopoulos
OBJECTIVE: Atherosclerosis is an age-related disease characterized by systemic oxidative stress and low-grade inflammation. The role of telomerase and telomere length in atherogenesis remains contentious. Short telomeres of peripheral leukocytes are predictive for coronary artery disease. Conversely, attenuated telomerase has been demonstrated to be protective for atherosclerosis. Hence, a potential causative role of telomerase in atherogenesis is critically debated. APPROACH AND RESULTS: In this study, we used multiple mouse models to investigate the regulation of telomerase under oxidative stress as well as its impact on atherogenesis in vitro and in vivo...
March 29, 2018: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/29593811/expression-of-selected-genes-of-dendritic-and-treg-cells-in-blood-and-skin-of-morphea-patients-treated-with-uva1-phototherapy
#18
Agnieszka J Osmola-Mańkowska, Ewa Teresiak-Mikołajczak, Michał J Kowalczyk, Ryszard W Żaba, Zygmunt Adamski, Aleksandra Dańczak-Pazdrowska
Introduction: Morphea is a chronic autoimmune disease characterized by fibrosis of the skin. Dendritic cells (DC) and regulatory T cells (Tregs) play a significant role in development of autoimmune and tolerance mechanisms. The aim of the study was to establish the expression of selected genes of plasmacytoid and myeloid DC, Treg cells, and the microenvironment of cytokines (interleukin-17A (IL-17A), transforming growth factor β (TGF-β)) in blood and skin of morphea patients. In addition, the effect of UVA1 phototherapy on expression of the aforementioned genes was evaluated...
March 2018: Archives of Medical Science: AMS
https://www.readbyqxmd.com/read/29593283/breast-and-pancreatic-cancer-interrupt-irf8-dependent-dendritic-cell-development-to-overcome-immune-surveillance
#19
Melissa A Meyer, John M Baer, Brett L Knolhoff, Timothy M Nywening, Roheena Z Panni, Xinming Su, Katherine N Weilbaecher, William G Hawkins, Cynthia Ma, Ryan C Fields, David C Linehan, Grant A Challen, Roberta Faccio, Rebecca L Aft, David G DeNardo
Tumors employ multiple mechanisms to evade immune surveillance. One mechanism is tumor-induced myelopoiesis, whereby the expansion of immunosuppressive myeloid cells can impair tumor immunity. As myeloid cells and conventional dendritic cells (cDCs) are derived from the same progenitors, we postulated that myelopoiesis might impact cDC development. The cDC subset, cDC1, which includes human CD141+ DCs and mouse CD103+ DCs, supports anti-tumor immunity by stimulating CD8+ T-cell responses. Here, to understand how cDC1 development changes during tumor progression, we investigated cDC bone marrow progenitors...
March 28, 2018: Nature Communications
https://www.readbyqxmd.com/read/29593222/cd4-and-cd8-t-cells-exert-regulatory-properties-during-experimental-acute-aristolochic-acid-nephropathy
#20
Thomas Baudoux, Cécile Husson, Eric De Prez, Inès Jadot, Marie-Hélène Antoine, Joëlle L Nortier, Jean-Michel Hougardy
Experimental aristolochic acid nephropathy is characterized by transient acute proximal tubule necrosis and inflammatory cell infiltrates followed by interstitial fibrosis and tubular atrophy. The respective role of T-cell subpopulations has never been studied in the acute phase of the mouse model, and was heretofore exclusively investigated by the use of several depletion protocols. As compared to mice injected with aristolochic acids alone, more severe acute kidney injury was observed after CD4+ or CD8+ T-cells depletion...
March 28, 2018: Scientific Reports
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