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https://www.readbyqxmd.com/read/28542882/butyrate-and-retinoic-acid-synergistically-imprint-mucosal-like-dendritic-cell-development-from-bone-marrow-cells
#1
Yetao Qiang, Jie Xu, Cheng Yan, Huimin Jin, Tengfei Xiao, Nannan Yan, Liping Zhou, Huazhang An, Xiaoming Zhou, Qixiang Shao, Sheng Xia
Accumulating data show that the phenotypes and functions of distinctive mucosal dendritic cells (DCs) in the gut are regulated by retinoic acid (RA). Unfortunately, the exact role of butyrate in RA mediated mucosal DC differentiation has not been thoroughly elucidated to date. Mucosal like dendritic cell differentiation was completed in vitro by culturing bone marrow cells with growth factors (GM-CSF/IL-4), RA and/or butyrate. The phenotypes, cytokine secretion, immune functions and levels of retinal dehydrogenase of different DCs were detected using qPCR, ELISA and flow cytometry, respectively...
May 24, 2017: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/28542574/combination-therapy-of-cancer-with-cancer-vaccine-and-immune-checkpoint-inhibitors-a-mathematical-model
#2
Xiulan Lai, Avner Friedman
In this paper we consider a combination therapy of cancer. One drug is a vaccine which activates dendritic cells so that they induce more T cells to infiltrate the tumor. The other drug is a checkpoint inhibitor, which enables the T cells to remain active against the cancer cells. The two drugs are positively correlated in the sense that an increase in the amount of each drug results in a reduction in the tumor volume. We consider the question whether a treatment with combination of the two drugs at certain levels is preferable to a treatment by one of the drugs alone at 'roughly' twice the dosage level; if that is the case, then we say that there is a positive 'synergy' for this combination of dosages...
2017: PloS One
https://www.readbyqxmd.com/read/28536390/showing-the-way-oncolytic-adenoviruses-as-chaperones-of-immunostimulatory-adjuncts
#3
REVIEW
Jing Li Huang, Christopher J LaRocca, Masato Yamamoto
Oncolytic adenoviruses (OAds) are increasingly recognized as vectors for immunotherapy in the treatment of various solid tumors. The myriads of advantages of using adenovirus include targeted specificity upon infection and selective replication, which lead to localized viral burst, exponential spread of OAds, and antitumor effect. OAds can also induce a strong immune reaction due to the massive release of tumor antigens upon cytolysis and the presence of viral antigens. This review will highlight recent advances in adenoviral vectors expressing immunostimulatory effectors, such as GM-CSF (granulocyte macrophage colony-stimulating factor), interferon-α, interleukin-12, and CD40L...
September 19, 2016: Biomedicines
https://www.readbyqxmd.com/read/28536308/immune-correlates-of-gm-csf-and-melanoma-peptide-vaccination-in-a-randomized-trial-for-the-adjuvant-therapy-of-resected-high-risk-melanoma-e4697
#4
Lisa H Butterfield, Fengmin Zhao, Sandra Lee, Ahmad A Tarhini, Kim A Margolin, Richard L White, Michael Atkins, Gary I Cohen, Theresa L Whiteside, John M Kirkwood, David H Lawson
Purpose: E4697 was a multi-center intergroup randomized placebo-controlled Phase III trial of adjuvant GM-CSF and/or a multi-epitope melanoma peptide vaccine for patients with completely resected, high-risk stage III/IV melanoma. <p>Experimental Design: 815 patients were enrolled from 12/99 to 10/06 into this 6-arm study. GM-CSF was chosen to promote the numbers and functions of dendritic cells (DC). The melanoma antigen peptide vaccine (Tyrosinase368-376 (370D), gp100209-217 (210M), MART-127-35) in Montanide was designed to promote melanoma specific CD8(+) T cell responses...
May 23, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28535995/inflammation-associated-gene-expression-in-raw-264-7-macrophages-induced-by-toxins-from-fungi-common-on-damp-building-materials
#5
Thomas G Rand, Carolyn T Chang, David R McMullin, J David Miller
Most fungi that grow on damp building materials produce low molecular weight compounds, some of which are known to be toxic. In this study, we tested the hypothesis that exposure to some metabolites of fungi common on damp building materials would result in time-, dose-, and compound-specific responses in the production of various chemokines by RAW 264.7 cells. Cell cultures were exposed to a 10(-7)M or 10(-8)M metabolite dose for 2, 4, 12 or 24h. Metabolite concentrations used were based on those that might be expected in alveolar macrophages due to inhalation exposure from living or working in a damp building...
May 20, 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/28534709/mdscs-are-involved-in-the-protumorigenic-potentials-of-gm-csf-in-colitis-associated-cancer
#6
Ning Ma, Qilin Liu, Lin Hou, Yalin Wang, Ziling Liu
Chronic inflammation is thought to be a major driving force for the development of colitis-associated colorectal cancer (CAC). As one member of proinflammatory cytokine family, granulocyte macrophage colony-stimulating factor (GM-CSF) has been identified to play a key role in CAC pathogenesis recently. The underlying mechanisms, however, remain largely unknown. In this study, we found that myeloid-derived suppressor cells (MDSCs) accumulated increasingly in the lesions during the progression from colitis to cancer, which was critical for CAC formation...
May 1, 2017: International Journal of Immunopathology and Pharmacology
https://www.readbyqxmd.com/read/28534275/sex-bias-in-pathogenesis-of-autoimmune-neuroinflammation-relevance-for-dimethyl-fumarate-immunomodulatory-anti-oxidant-action
#7
Zorica Stojić-Vukanić, Jelena Kotur-Stevuljević, Mirjana Nacka-Aleksić, Duško Kosec, Ivana Vujnović, Ivan Pilipović, Mirjana Dimitrijević, Gordana Leposavić
In the present study, upon showing sexual dimorphism in dimethyl fumarate (DMF) efficacy to moderate the clinical severity of experimental autoimmune encephalomyelitis (EAE) in Dark Agouti rats, cellular and molecular substrate of this dimorphism was explored. In rats of both sexes, DMF administration from the day of immunization attenuated EAE severity, but this effect was more prominent in males leading to loss of the sexual dimorphism observed in vehicle-administered controls. Consistently, in male rats, DMF was more efficient in diminishing the number of CD4+ T lymphocytes infiltrating spinal cord (SC) and their reactivation, the number of IL-17+ T lymphocytes and particularly cellularity of their highly pathogenic IFN-γ+GM-CSF+IL-17+ subset...
May 22, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28534038/analysis-of-mitochondrial-transfer-in-direct-co-cultures-of-human-monocyte-derived-macrophages-mdm-and-mesenchymal-stem-cells-msc
#8
Megan V Jackson, Anna D Krasnodembskaya
Mesenchymal stem/stromal cells (MSC) are adult stem cells which have been shown to improve survival, enhance bacterial clearance and alleviate inflammation in pre-clinical models of acute respiratory distress syndrome (ARDS) and sepsis. These diseases are characterised by uncontrolled inflammation often underpinned by bacterial infection. The mechanisms of MSC immunomodulatory effects are not fully understood yet. We sought to investigate MSC cell contact-dependent communication with alveolar macrophages (AM), professional phagocytes which play an important role in the lung inflammatory responses and anti-bacterial defence...
May 5, 2017: Bio-protocol
https://www.readbyqxmd.com/read/28533230/deletion-of-pikfyve-alters-alveolar-macrophage-populations-and-exacerbates-allergic-inflammation-in-mice
#9
Takumi Kawasaki, Kosuke Ito, Haruhiko Miyata, Shizuo Akira, Taro Kawai
Alveolar macrophages (AMs) are specialized tissue-resident macrophages that orchestrate the immune responses to inhaled pathogens and maintain organ homeostasis of the lung. Dysregulation of AMs is associated with allergic inflammation and asthma. Here, we examined the role of a phosphoinositide kinase PIKfyve in AM development and function. Mice with conditionally deleted PIKfyve in macrophages have altered AM populations. PIKfyve deficiency results in a loss of AKT activation in response to GM-CSF, a cytokine critical for AM development...
May 22, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28533221/cd9-regulates-mhc-ii-trafficking-in-monocyte-derived-dendritic-cells
#10
Vera Rocha-Perugini, Gloria Martínez Del Hoyo, José Maria González-Granado, Marta Ramírez-Huesca, Virginia Zorita, Eric Rubinstein, Claude Boucheix, Francisco Sánchez-Madrid
Antigen presentation by dendritic cells (DCs) stimulates naïve CD4(+) T cells, triggering T cell activation and the adaptive arm of the immune response. Newly synthesized major histocompatibility complex class II molecules (MHC-II) accumulate at MHC-II-enriched endosomal compartments, and are transported to the plasma membrane of DCs after binding to antigenic peptides to enable antigen presentation. In DCs, MHC-II molecules are included in tetraspanin-enriched microdomains (TEMs). However, the role of tetraspanin CD9 in these processes remains largely undefined...
May 22, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28530155/an-oncolytic-adenovirus-encoding-decorin-and-gm-csf-inhibits-tumor-growth-in-a-colorectal-tumor-model-by-targeting-pro-tumorigenic-signals-and-via-immune-activation
#11
Zhao Liu, Yuefeng Yang, Xiaoyan Zhang, Hao Wang, Weidong Xu, Hua Wang, FengJun Xiao, Zhigang Bai, Hongwei Yao, Xuemei Ma, Lan Jin, Chu-Tse Wu, Prem Seth, Zhongtao Zhang, Lisheng Wang
In advanced and metastatic stages of colorectal cancer (CRC), reduced sensitivity to conventional strategies is still a major obstacle to successful treatments. Decorin is an important regulator in the development and progression of various cancers. To examine if CRC patients have altered decorin levels, expression of decorin and its target genes, Met and vascular endothelial growth factor A (VEGFA) were analyzed in their tumors. Compared to normal tissues, decorin expression was reduced in CRC patients' tumors, while, there were increased Met and VEGFA levels...
May 20, 2017: Human Gene Therapy
https://www.readbyqxmd.com/read/28522600/frontline-science-nasal-epithelial-gm-csf-contributes-to-tlr5-mediated-modulation-of-airway-dendritic-cells-and-subsequent-iga-response
#12
Yuan Cao, Ejuan Zhang, Jingyi Yang, Yi Yang, Jie Yu, Yang Xiao, Wei Li, Dihan Zhou, Yaoming Li, Bali Zhao, Hu Yan, Mengji Lu, Maohua Zhong, Huimin Yan
Flagellin, as a TLR5 agonist, is an established mucosal adjuvant for enhancing mucosal IgA responses by i.n. immunization. Nasal epithelial cells (NECs) are the first sentinel cells to be exposed to antigen and adjuvant in i.n. immunization, and it is suggested that they play an important role in the mucosal adjuvant activity of flagellin. However, the molecular mechanism leading to modulation and the response by flagellin-activated NECs remain unknown. We aimed to identify the soluble mediator(s) from flagellin-activated NECs that modulate the functions of airway dendritic cells (DCs) and enhance subsequent IgA response...
May 18, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28515356/licensing-delineates-helper-and-effector-nk-cell-subsets-during-viral-infection
#13
Anthony E Zamora, Ethan G Aguilar, Can M Sungur, Lam T Khuat, Cordelia Dunai, G Raymond Lochhead, Juan Du, Claire Pomeroy, Bruce R Blazar, Dan L Longo, Jeffrey M Venstrom, Nicole Baumgarth, William J Murphy
Natural killer (NK) cells can be divided into phenotypic subsets based on expression of receptors that bind self-MHC-I molecules, a concept termed licensing or education. Here we show NK cell subsets with different migratory, effector, and immunoregulatory functions in dendritic cell and antigen (ag)-specific CD8+ T cell responses during influenza and murine cytomegalovirus infections. Shortly after infection, unlicensed NK cells localized in draining lymph nodes and produced GM-CSF, which correlated with the expansion and activation of dendritic cells, and resulted in greater and sustained ag-specific T cell responses...
May 18, 2017: JCI Insight
https://www.readbyqxmd.com/read/28514019/does-dust-associated-pulmonary-alveolar-proteinosis-represent-an-autoimmune-disorder
#14
Bilge Uzmezoglu, Cebrail Simsek, Sevtap Gulgosteren, Berna E Gebesoglu
The role of autoantibodies against granulocyte-macrophage colony-stimulating factor (GM-CSF) in the development of secondary pulmonary alveolar proteinosis (PAP) in patients exposed to occupational and environmental dust remains unclear. Herein, we describe two cases of secondary PAP who had GM-CSF antibodies and absence of STAT5 phosphorylation index, suggestive of a potential relationship between the appearance of GM-CSF antibodies and environmental dust exposure. However, whether the presence of GM-CSF antibodies is a part of the pathological process or represents an epiphenomenon is currently unknown...
June 2017: American Journal of Industrial Medicine
https://www.readbyqxmd.com/read/28513595/hiv-2-infection-is-associated-with-preserved-galt-homeostasis-and-epithelial-integrity-despite-ongoing-mucosal-viral-replication
#15
S M Fernandes, A R Pires, P Matoso, C Ferreira, H Nunes-Cabaço, L Correia, E Valadas, J Poças, P Pacheco, H Veiga-Fernandes, R B Foxall, A E Sousa
The mechanisms that enable preservation of gut mucosal integrity during persistent viral replication and inherent inflammation remain unclear. Here, we investigated, for the first time, gut homeostasis in HIV-2 infection, a naturally occurring form of attenuated HIV disease. We found viral replication in both sigmoid and ileum of asymptomatic HIV-2+ patients (range: 240-851 circulating CD4+T-cells per μl) despite their undetectable viremia, accompanied by interferon-γ-producing CD8 T-cell expansion, irrespective of antiretroviral treatment...
May 17, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/28512190/hematopoietic-origin-of-langerhans-cell-histiocytosis-and-erdheim-chester-disease-in-adults
#16
Paul Milne, Venetia Bigley, Chris M Bacon, Antoine Néel, Naomi McGovern, Simon Bomken, Muzlifah Haniffa, Eli L Diamond, Benjamin H Durham, Johannes Visser, David Hunt, Harsha Gunawardena, Mac Macheta, Kenneth L McClain, Carl Allen, Omar Abdel-Wahab, Matthew Collin
Langerhans cell histiocytosis (LCH) and Erdheim Chester Disease (ECD) are rare histiocytic disorders induced by somatic mutation of MAP kinase pathway genes. BRAF(V600E) mutation is the most common mutation in both conditions and also occurs in the hematopoietic neoplasm hairy cell leukemia (HCL). It is not known if adult LCH or ECD arise from hematopoietic stem cells (HSC) nor which potential blood borne precursors lead to the formation of histiocytic lesions. In this study, BRAF V600E allele-specific PCR was used to map the neoplastic clone in 20 adults with LCH ECD and HCL...
May 16, 2017: Blood
https://www.readbyqxmd.com/read/28507788/adaptive-t-cell-responses-induced-by-oncolytic-herpes-simplex-virus-granulocyte-macrophage-colony-stimulating-factor-therapy-expanded-by-dendritic-cell-and-cytokine-induced-killer-cell-adoptive-therapy
#17
Jun Ren, William R Gwin, Xinna Zhou, Xiaoli Wang, Hongyan Huang, Ni Jiang, Lei Zhou, Pankaj Agarwal, Amy Hobeika, Erika Crosby, Zachary C Hartman, Michael A Morse, Kevin H Eng, H Kim Lyerly
Purpose: Although local oncolytic viral therapy (OVT) may enhance tumor lysis, antigen release, and adaptive immune responses, systemic antitumor responses post-therapy are limited. Adoptive immunotherapy with autologous dendritic cells (DC) and cytokine-induced killer cells (DC-CIK) synergizes with systemic therapies. We hypothesized that OVT with Herpes Simplex Virus-granulocyte macrophage-colony-stimulating factor (HSV-GM-CSF) would induce adaptive T cell responses that could be expanded systemically with sequential DC-CIK therapy...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28507543/long-term-monocyte-dysfunction-after-sepsis-in-humanized-mice-is-related-to-persisted-activation-of-macrophage-colony-stimulation-factor-m-csf-and-demethylation-of-pu-1-and-it-can-be-reversed-by-blocking-m-csf-in-vitro-or-by-transplanting-na%C3%A3-ve-autologous
#18
Natalia Lapko, Mateusz Zawadka, Jacek Polosak, George S Worthen, Gwenn Danet-Desnoyers, Monika Puzianowska-Kuźnicka, Krzysztof Laudanski
The duration of post-sepsis long-term immune suppression is poorly understood. Here, we focused on the role of monocytes (MO) as the pivotal cells for long-term regulation of post-sepsis milieu. Lost ability of MO to adapt is seen in several acute conditions, but it is unclear for how long MO aberrancy post-sepsis can persist. Interestingly, the positive feedback loop sustaining secretion of macrophage-colony stimulation factor (M-CSF) can persist even after resolution of sepsis and significantly alters performance of MO...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28505356/distinct-th1-and-th2-cellular-responses-associated-with-malaria-protection-and-risk-in-rts-s-as01e-vaccinees
#19
Gemma Moncunill, Maxmillian Mpina, Augusto J Nhabomba, Ruth Aguilar, Aintzane Ayestaran, Héctor Sanz, Joseph J Campo, Chenjerai Jairoce, Diana Barrios, Yan Dong, Núria Díez-Padrisa, José F Fernandes, Salim Abdulla, Jahit Sacarlal, Nana A Williams, Jaroslaw Harezlak, Benjamin Mordmüller, Selidji T Agnandji, John J Aponte, Claudia Daubenberger, Clarissa Valim, Carlota Dobaño
Background.: The RTS,S/AS01E malaria vaccine has moderate efficacy, lower in infants than children. Current efforts to enhance RTS,S/AS01E efficacy would benefit from learning about the vaccine-induced immunity and identifying correlates of malaria protection, which could, for instance, inform the choice of adjuvants. Here, we sought cellular immunity-based correlates of malaria protection and risk associated with RTS,S/AS01E vaccination. Methods.: We performed a matched case-control study nested within the multicenter African RTS,S/AS01E Phase III trial...
May 13, 2017: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
https://www.readbyqxmd.com/read/28500302/different-polyubiquitinated-bodies-in-human-dendritic-cells-il-4-causes-pacs-during-differentiation-while-lps-or-ifn%C3%AE-induces-dalis-during-maturation
#20
Daniela Montagna, Patrizia Sommi, Vittorio Necchi, Agostina Vitali, Enrica Montini, Ilaria Turin, Daniela Ferraro, Vittorio Ricci, Enrico Solcia
Two types of polyubiquitin-reactive cytoplasmic bodies, particulate cytoplasmic structures (PaCS) and dendritic cell (DC) aggresome-like induced structures (DALIS), were analyzed by electron microscopy, immunocytochemistry, immunoblotting, and flow cytometry in DC obtained from human blood monocytes incubated with GM-CSF plus IL-4 (IL4-DC), GM-CSF plus IFNα (IFN-DC), or GM-CSF alone (GM-DC), with or without LPS maturation. PaCS developed as monomorphic aggregates of proteasome-reactive barrel-like particles only in ribosomes-rich cytoplasmic areas of differentiating IL4-DC...
May 12, 2017: Scientific Reports
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