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https://www.readbyqxmd.com/read/27933701/ccr2-mediates-helicobacter-pylori-induced-immune-tolerance-and-contributes-to-mucosal-homeostasis
#1
Xia Sun, Min Zhang, Mohamad El-Zaatari, Gray B Huffnagle, John Y Kao
BACKGROUND: We previously demonstrated that H. pylori infection leads to increased induction of regulatory T cells in local and systemic immune compartments. Here, we investigate the role of CCR2 in the tolerogenic programing of dendritic cells in a mouse model of H. pylori infection. MATERIALS AND METHODS: CCR2 deficient (CCR2KO) mice and wild-type (Wt) mice infected with H. pylori SS1 strain were analyzed by qPCR and FACS analysis. In vitro, bone marrow-derived DC on day 6 from CCR2KO and Wt mice cocultured with or without H...
December 8, 2016: Helicobacter
https://www.readbyqxmd.com/read/27933310/dynamics-of-antigen-presentation-to-transgene-product-specific-cd4-t-cells-and-of-treg-induction-upon-hepatic-aav-gene-transfer
#2
George Q Perrin, Irene Zolotukhin, Alexandra Sherman, Moanaro Biswas, Ype P de Jong, Cox Terhorst, Andrew M Davidoff, Roland W Herzog
The tolerogenic hepatic microenvironment impedes clearance of viral infections but is an advantage in viral vector gene transfer, which often results in immune tolerance induction to transgene products. Although the underlying tolerance mechanism has been extensively studied, our understanding of antigen presentation to transgene product-specific CD4(+) T cells remains limited. To address this, we administered hepatotropic adeno-associated virus (AAV8) vector expressing cytoplasmic ovalbumin (OVA) into wt mice followed by adoptive transfer of transgenic OVA-specific T cells...
2016: Molecular Therapy. Methods & Clinical Development
https://www.readbyqxmd.com/read/27932175/first-attempt-of-sequential-living-donor-liver-and-hematopoietic-stem-cell-transplantation-in-a-child-with-advanced-hepatocellular-carcinoma-case-report
#3
J A Picoraro, N Ovchinsky, M Martinez, S J Lobritto, P Satwani, R Ramphal, M S Cairo, T Kato
Effective therapeutic options for advanced hepatocellular carcinoma are limited. Hematopoietic stem cell transplantation may offer a graft-versus-tumor effect. Combined liver and hematopoietic stem cell transplantation from the same donor with preparatory conditioning may promote tolerogenicity to the liver allograft and offers the potential for immunosuppression withdrawal. We report our experience with the use of this approach in a pediatric patient with invasive hepatocellular carcinoma and pulmonary metastases who underwent a living-donor liver transplantation followed by reduced-toxicity myeloablative conditioning and hematopoietic stem cell transplant from the same parental donor...
November 2016: Transplantation Proceedings
https://www.readbyqxmd.com/read/27931844/dendritic-cells-in-hematological-malignancies
#4
REVIEW
Domenico Galati, Gaetano Corazzelli, Rosaria De Filippi, Antonio Pinto
Dendritic cells (DCs) are bone-marrow-derived immune cells accounted for a crucial role in initiating and modulating the adaptive immune response and supporting the innate immune response independently from T cells. While functioning as the most effective antigen-presenting cells within the immune system, DCs can otherwise induce tolerance in central and peripheral lymphoid organs acting therefore as suppressors rather than stimulators of the immune response. Within mechanisms regulating antitumor immunity, DCs can capture antigens from viable or damaged tumor cells and present the processed peptides to T-cells to prompt the generation and maintenance of an effective tumor-specific T-cell response...
December 2016: Critical Reviews in Oncology/hematology
https://www.readbyqxmd.com/read/27928097/intestinal-immunity-and-gut-microbiota-in-atherogenesis
#5
Tomoya Yamashita
Atherosclerosis is a chronic inflammatory disease. Interventions targeting the inflammatory process could provide new strategies for preventing atherosclerotic cardiovascular diseases (CVD). Previously, we have reported that oral administration of anti-CD3 antibodies, or active vitamin D3, reduced atherosclerosis in mice via recruiting regulatory T cells and tolerogenic dendritic cells to the gut-associated lymphoid tissues. From this, it is reasonable to propose that the intestine could be a novel therapeutic target for prevention of atherosclerotic CVD...
December 7, 2016: Journal of Atherosclerosis and Thrombosis
https://www.readbyqxmd.com/read/27927966/tolerogenic-dendritic-cells-from-poorly-compensated-type-1-diabetes-patients-have-decreased-ability-to-induce-stable-antigen-specific-t-cell-hyporesponsiveness-and-generation-of-suppressive-regulatory-t-cells
#6
Klára Dáňová, Anna Grohová, Pavla Strnadová, David P Funda, Zdeněk Šumník, Jan Lebl, Ondřej Cinek, Štěpánka Průhová, Stanislava Koloušková, Barbora Obermannová, Lenka Petruželková, Anna Šedivá, Petra Fundová, Karsten Buschard, Radek Špíšek, Lenka Palová-Jelínková
Tolerogenic dendritic cells (tolDCs) may offer an interesting intervention strategy to re-establish Ag-specific tolerance in autoimmune diseases, including type 1 diabetes (T1D). T1D results from selective destruction of insulin-producing β cells leading to hyperglycemia that, in turn, specifically affects a patient's immune system. In this study, we prepared monocyte-derived tolDCs modulated by dexamethasone and vitamin D2 from 31 T1D patients with optimal glycemic control and 60 T1D patients with suboptimal glycemic control and assessed their tolerogenic properties in correlation with metabolic state of patients...
December 7, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27919929/interleukin-37-and-dendritic-cells-treated-with-interleukin-37-plus-troponin-i-ameliorate-cardiac-remodeling-after-myocardial-infarction
#7
Ruirui Zhu, Haitao Sun, Kunwu Yu, Yucheng Zhong, Huairui Shi, Yuzhen Wei, Xin Su, Wenbin Xu, Quan Luo, Fangyuan Zhang, Zhengfeng Zhu, Kai Meng, Xiaoqi Zhao, Yuzhou Liu, Yi Mao, Peng Cheng, Xiaobo Mao, Qiutang Zeng
BACKGROUND: Excessive immune-mediated inflammatory reactions play a deleterious role in postinfarction ventricular remodeling. Interleukin-37 (IL-37) emerges as an inhibitor of both innate and adaptive immunity. However, the exact role of IL-37 and IL-37 plus troponin I (TnI)-treated dendritic cells (DCs) in ventricular remodeling after myocardial infarction (MI) remains elusive. METHODS AND RESULTS: MI was induced by permanent ligation of the left anterior descending artery...
December 5, 2016: Journal of the American Heart Association
https://www.readbyqxmd.com/read/27908931/filling-the-tank-keeping-antitumor-t-cells-metabolically-fit-for-the-long-haul
#8
REVIEW
Greg M Delgoffe
Discoveries in tumor immunology and subsequent clinical advances in cancer immunotherapy have revealed that the immune system is not oblivious to tumor progression but heavily interacts with developing neoplasia and malignancy. A major factor preventing immune destruction is the establishment of a highly immunosuppressive tumor microenvironment (TME), which provides architecture to the tumor, supports indirect means of immunosuppression such as the recruitment of tolerogenic cells like regulatory T cells and myeloid-derived suppressor cells (MDSC), and represents a zone of metabolically dearth conditions...
December 2016: Cancer Immunology Research
https://www.readbyqxmd.com/read/27903843/downregulation-of-l-arginine-metabolism-in-dendritic-cells-induces-tolerance-to-exogenous-antigen
#9
Patricia U Simioni, Luis Gr Fernandes, Wirla Msc Tamashiro
Dendritic cells (DC) are potential tools for therapeutic applications and several strategies to generate tolerogenic DCs are under investigation. When activated by cytokines and microbial products, DCs express mediators that modulate immune responses. In this regard, the metabolites generated by the activities of inducible nitric oxide synthase (iNOS) and arginase in DCs seem to play important roles. Here, we evaluated the effects of adoptive transfer of DCs generated in vitro from bone marrow precursors (BMDC) modulated with L-NAME (Nω-nitro-L-arginine methyl ester) and NOHA (NG-Hydroxy-L-arginine), inhibitors of iNOS and arginase, respectively, upon the immune response of the wild type (BALB/c) and OVA-TCR transgenic (DO11...
November 30, 2016: International Journal of Immunopathology and Pharmacology
https://www.readbyqxmd.com/read/27895621/immune-modulatory-effects-of-human-chorionic-gonadotropin-on-dendritic-cells-supporting-fetal-survival-in-murine-pregnancy
#10
Dominique Dauven, Stefanie Ehrentraut, Stefanie Langwisch, Ana Claudia Zenclussen, Anne Schumacher
Dendritic cells (DCs) are critically involved in the determination of immunity vs. tolerance. Hence, DCs are key regulators of immune responses either favoring or disfavoring fetal survival. Several factors were proposed to modulate DC phenotype and function during pregnancy. Here, we studied whether the pregnancy hormone human chorionic gonadotropin (hCG) is involved in DC regulation. In vitro, bone marrow-derived DCs (BMDCs) were stimulated in the presence or absence of urine-purified or recombinant hCG (rhCG) preparations...
2016: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/27890914/dendritic-cell-migration-in-health-and-disease
#11
Tim Worbs, Swantje I Hammerschmidt, Reinhold Förster
Dendritic cells (DCs) are potent and versatile antigen-presenting cells, and their ability to migrate is key for the initiation of protective pro-inflammatory as well as tolerogenic immune responses. Recent comprehensive studies have highlighted the importance of DC migration in the maintenance of immune surveillance and tissue homeostasis, and also in the pathogenesis of a range of diseases. In this Review, we summarize the anatomical, cellular and molecular factors that regulate the migration of different DC subsets in health and disease...
November 28, 2016: Nature Reviews. Immunology
https://www.readbyqxmd.com/read/27889479/ido1-is-an-integral-mediator-of-inflammatory-neovascularization
#12
Arpita Mondal, Courtney Smith, James B DuHadaway, Erika Sutanto-Ward, George C Prendergast, Arturo Bravo-Nuevo, Alexander J Muller
The immune tolerogenic effects of IDO1 (indoleamine 2,3-dioxygenase 1) have been well documented and genetic studies in mice have clearly established the significance of IDO1 in tumor promotion. Dichotomously, the primary inducer of IDO1, the inflammatory cytokine IFNγ (interferon-γ), is a key mediator of immune-based tumor suppression. One means by which IFNγ can exert an anti-cancer effect is by decreasing tumor neovascularization. We speculated that IDO1 might contribute to cancer promotion by countering this anti-neovascular effect of IFNγ, possibly through IDO1-potentiated elevation of the pro-tumorigenic inflammatory cytokine IL6 (interleukin-6)...
November 9, 2016: EBioMedicine
https://www.readbyqxmd.com/read/27888555/renal-operational-tolerance-is-associated-with-a-defect-of-blood-tfh-cells-that-exhibit-impaired-b-cell-help
#13
Alexis Chenouard, Mélanie Chesneau, Linh Bui Nguyen, Sabine Le Bot, Marion Cadoux, Emilie Dugast, Chloé Paul, Stéphanie Malard-Castagnet, Simon Ville, Pierrick Guérif, Jean-Paul Soulillou, Nicolas Degauque, Richard Danger, Magali Giral, Sophie Brouard
Renal operationally tolerant patients (TOL) display a defect in B cell differentiation, with a deficiency in plasma cells. Recently described, T follicular helper cells (Tfh) play a critical role in B cell differentiation. We analyzed blood Tfh subsets in TOL and transplanted patients with stable graft function under immunosuppression (STA). We observed a reduced proportion of blood activated and highly functional Tfh subsets in TOL, without affecting Tfh absolute numbers. Functionally, Tfh from TOL displayed a modified gene expression profile, failed to produce IL-21 and were unable to induce IgG production by naive B cells...
November 26, 2016: American Journal of Transplantation
https://www.readbyqxmd.com/read/27867515/the-cd8-t-cell-response-during-tolerance-induction-in-liver-transplantation
#14
REVIEW
Yik Chun Wong, Geoffrey W McCaughan, David G Bowen, Patrick Bertolino
Both experimental and clinical studies have shown that the liver possesses unique tolerogenic properties. Liver allografts can be spontaneously accepted across complete major histocompatibility mismatch in some animal models. In addition, some liver transplant patients can be successfully withdrawn from immunosuppressive medications, developing 'operational tolerance'. Multiple mechanisms have been shown to be involved in inducing and maintaining alloimmune tolerance associated with liver transplantation. Here, we focus on CD8 T-cell tolerance in this setting...
October 2016: Clinical & Translational Immunology
https://www.readbyqxmd.com/read/27864897/tolerogenic-dendritic-cell-therapy-in-organ-transplantation
#15
REVIEW
Aurélie Moreau, Brigitte Alliot-Licht, Maria-Cristina Cuturi, Gilles Blancho
Although the occurrence of acute rejection was significantly reduced and the allograft survival at one year was massively improved by the development of pharmacological immunosuppressive drugs, little progress has been made regarding long-term graft survival. Cell therapy appears to be an innovative and promising strategy to minimize the use of immunosuppression in transplantation and consequently increases long-term graft survival. The strength of cell therapy is that it will induce graft-specific tolerance and not a general immunosuppression of the patients...
November 19, 2016: Transplant International: Official Journal of the European Society for Organ Transplantation
https://www.readbyqxmd.com/read/27861999/forkhead-box-protein-3-foxp3-producing-dendritic-cells-suppress-allergic-response
#16
Xiao-Yu Liu, Ling-Zhi Xu, Xiang-Qian Luo, Xiao-Rui Geng, Zhi-Qiang Liu, Li-Teng Yang, Gui Yang, Si Chen, Zhi-Gang Liu, Hua-Bin Li, Li-Tao Yang, Tian-Gang Luan, Ping-Chang Yang
BACKGROUND: The generation of the tolerogenic dendritic cells (DC) is not fully understood yet. Forkhead box protein-3 (Foxp3) is an important molecule in the immune tolerance. This study tests a hypothesis that DCs express Foxp3, which can be up regulated by Staphylococcal enterotoxin B (SEB). METHODS: The expression of Foxp3 by DCs was evaluated by real time RT-PCR, Western blotting, flow cytometry and chromatin immunoprecipitation assay. RESULTS: We observed that mice treated with SEB at 0...
November 15, 2016: Allergy
https://www.readbyqxmd.com/read/27859049/lps-primed-heterotolerant-dendritic-cells-suppress-experimental-autoimmune-uveoretintitis-by-multiple-mechanisms
#17
Izabela P Klaska, Elizabeth Muckersie, Cristina Martin-Granados, Maria Christofi, John V Forrester
Exposure of bone marrow derived dendritic cells (BMDC) to high dose ultrapure lipopolysaccharide for 24 hours (h) (LPS-primed BMDC) enhances their potency in preventing inter-photoreceptor retinoid binding protein (IRBP): complete Freund's adjuvant (CFA)-induced experimental autoimmune uveoretinitis (EAU). LPS-primed BMDC are refractory to further exposure to LPS (= endotoxin tolerance, ET), evidenced here by decreased phosphorylation of TANK-binding kinase 1 (TBK1), interferon regulatory factor 3 (IRF3), c-Jun N-terminal kinase (JNK), and p38 mitogen-activated protein kinase (p38 MAPK) as well as impaired nuclear translocation of nuclear factor κB (NF-κB) and IRF3, resulting in reduced tumor necrosis factor alpha (TNF-α), interleukin (IL)-6, IL-12 and interferon beta (IFN-β) secretion...
November 15, 2016: Immunology
https://www.readbyqxmd.com/read/27857212/gr-independent-down-modulation-on-gm-csf-bone-marrow-derived-dendritic-cells-by-the-selective-glucocorticoid-receptor-modulator-compound-a
#18
Andres E Barcala Tabarrozzi, Luz Andreone, Julie Deckers, Carla N Castro, María L Gimeno, Laura Ariolfo, Paula M Berguer, María Antunica-Noguerol, Ana C Liberman, Sabine Vettorazzi, Jan P Tuckermann, Karolien De Bosscher, Marcelo J Perone
Dendritic cells (DC) initiate the adaptive immune response. Glucocorticoids (GCs) down-modulate the function of DC. Compound A (CpdA, (2-(4-acetoxyphenyl)-2-chloro-N-methyl-ethylammonium chloride) is a plant-derived GR-ligand with marked dissociative properties. We investigated the effects of CpdA on in vitro generated GM-CSF-conditioned bone marrow-derived DC (BMDC). CpdA-exposed BMDC exhibited low expression of cell-surface molecules and diminution of the release of proinflammatory cytokines upon LPS stimulation; processes associated with BMDC maturation and activation...
November 18, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27855508/bioanalytical-qualification-of-clinical-biomarker-assays-in-plasma-using-a-novel-multi-analyte-simple-plex-%C3%A2-platform
#19
Vinita Gupta, Teresa Davancaze, Jeremy Good, Navdeep Kalia, Michael Anderson, Jeffrey J Wallin, Ann Brady, An Song, Wenfeng Xu
AIM: Immune-checkpoint inhibitors are presumed to break down the tolerogenic state of immune cells by activating T-lymphocytes that release cytokines and enhance effector cell function for elimination of tumors. Measurement of cytokines is being pursued for better understanding of the mechanism of action of immune-checkpoint inhibitors, as well as to identify potential predictive biomarkers. RESULTS: In this study, we show bioanalytical qualification of cytokine assays in plasma on a novel multi-analyte immunoassay platform, Simple Plex(™)...
December 2016: Bioanalysis
https://www.readbyqxmd.com/read/27833846/mesenchymal-stromal-cells-derived-from-whole-human-umbilical-cord-exhibit-similar-properties-to-those-derived-from-wharton-s-jelly-and-bone-marrow
#20
Claire Mennan, Sharon Brown, Helen McCarthy, Eleni Mavrogonatou, Dimitris Kletsas, John Garcia, Birender Balain, James Richardson, Sally Roberts
Mesenchymal stromal cells (MSC) can be isolated from several regions of human umbilical cords, including Wharton's jelly (WJ), artery, vein or cord lining. These MSC appear to be immune privileged and are promising candidates for cell therapy. However, isolating MSC from WJ, artery, vein or cord lining requires time-consuming tissue dissection. MSC can be obtained easily via briefly digesting complete segments of the umbilical cord, likely containing heterogenous or mixed populations of MSC (MC-MSC). MC-MSC are generally less well characterized than WJ-MSC, but nevertheless represent a potentially valuable population of MSC...
November 2016: FEBS Open Bio
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