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tolerogenic dc

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https://www.readbyqxmd.com/read/28096089/tolerogenic-interactions-between-cd8-dendritic-cells-and-nkt-cells-prevent-rejection-of-bone-marrow-and-organ-grafts
#1
David Hongo, Xiaobin Tang, Xiangyue Zhang, Edgar G Engleman, Samuel Strober
The combination of total lymphoid irradiation and anti-T cell antibodies safely induces immune tolerance to combined hematopoietic cell and organ allografts in humans. Our mouse model required host natural killer T (NKT) cells to induce tolerance. Since NKT cells normally depend on signals from CD8+ dendritic cells (DCs) for their activation, we used the mouse model to test the hypothesis that after lymphoid irradiation host CD8+DCs play a requisite role in tolerance induction through interactions with NKT cells...
January 17, 2017: Blood
https://www.readbyqxmd.com/read/28073842/expression-of-cd14-il-10-and-tolerogenic-signature-in-dendritic-cells-inversely-correlate-with-response-to-tarp-vaccination-in-prostate-cancer-patients
#2
Luciano Castiello, Marianna Sabatino, Jiaqiang Ren, Masaki Terabe, Hanh Khuu, Lauren V Wood, Jay A Berzofsky, David F Stroncek
PURPOSE: Despite the vast number of clinical trials conducted so far, Dendritic cell (DC)-based cancer vaccines have mostly shown unsatisfactory results. Factors and manufacturing procedures essential for these therapeutics to induce effective anti-tumor immune responses have yet to be fully characterized. We here aimed to identify DC markers correlating with clinical and immunological response in a prostate carcinoma vaccination regimen. EXPERIMENTAL DESIGN: We performed an extensive characterization of DCs used to vaccinate 18 prostate carcinoma patients enrolled in a pilot trial of TCR gamma alternate reading frame protein (TARP) peptide vaccination (NCT00908258)...
January 10, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28003813/context-specific-and-immune-cell-dependent-antitumor-activities-of-%C3%AE-1-antitrypsin
#3
Ofer Guttman, Gabriella S Freixo-Lima, Ziv Kaner, Yotam Lior, Peleg Rider, Eli C Lewis
α1-antitrypsin (AAT), a circulating glycoprotein that rises during acute phase responses and healthy pregnancies, exhibits immunomodulatory properties in several T-cell-dependent immune pathologies. However, AAT does not directly interfere with T-cell responses; instead, it facilitates polarization of macrophages and dendritic cells towards M2-like and tolerogenic cells, respectively. AAT also allows NK cell responses against tumor cells, while attenuating DC-dependent induction of autoimmune NK cell activities...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27973435/antithymocyte-globulin-induces-a-tolerogenic-phenotype-in-human-dendritic-cells
#4
Tobias Roider, Michael Katzfuß, Carina Matos, Katrin Singer, Kathrin Renner, Peter J Oefner, Katja Dettmer-Wilde, Wolfgang Herr, Ernst Holler, Marina Kreutz, Katrin Peter
Antithymocyte globulin (ATG) is used in the prevention of graft-versus-host disease during allogeneic hematopoietic stem cell transplantation. It is generally accepted that ATG mediates its immunosuppressive effect primarily via depletion of T cells. Here, we analyzed the impact of ATG-Fresenius (now Grafalon(®)) on human monocyte-derived dendritic cells (DC). ATG induced a semi-mature phenotype in DC with significantly reduced expression of CD14, increased expression of HLA-DR, and intermediate expression of CD54, CD80, CD83, and CD86...
December 11, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27933701/ccr2-mediates-helicobacter-pylori-induced-immune-tolerance-and-contributes-to-mucosal-homeostasis
#5
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/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/27903843/downregulation-of-l-arginine-metabolism-in-dendritic-cells-induces-tolerance-to-exogenous-antigen
#7
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
#8
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
#9
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...
January 2017: Nature Reviews. Immunology
https://www.readbyqxmd.com/read/27861999/forkhead-box-protein-3-foxp3-producing-dendritic-cells-suppress-allergic-response
#10
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/27857212/gr-independent-down-modulation-on-gm-csf-bone-marrow-derived-dendritic-cells-by-the-selective-glucocorticoid-receptor-modulator-compound-a
#11
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/27757296/inhibition-of-sirp%C3%AE-in-dendritic-cells-potentiates-potent-antitumor-immunity
#12
Qiong Liu, Wen Wen, Liang Tang, Chen-Jie Qin, Yan Lin, Hui-Lu Zhang, Han Wu, Charles Ashton, Hong-Ping Wu, Jin Ding, Wei Dong, Le-Xing Yu, Wen Yang, Dan-Dan Huang, Meng-Chao Wu, Hong-Yang Wang, He-Xin Yan
Despite their central function in tumor immunity, dendritic cells (DCs) can respond to inhibitory signals and become tolerogenic, curtailing T cell responses in vivo. Here, we provide the evidence for an inhibitory function of signal regulatory protein (SIRP) α in DC survival and activation. In tumors from human liver cancer patients, infiltrative DCs expressed elevated levels of SIRPα, which is correlated with the induction of immune tolerance within the tumors. Silencing of SIRPα resulted in a significant increase in the longevity of antigen-pulsed DCs in the draining lymph nodes...
2016: Oncoimmunology
https://www.readbyqxmd.com/read/27710838/bet-bromodomain-inhibition-reduces-maturation-and-enhances-tolerogenic-properties-of-human-and-mouse-dendritic-cells
#13
Ronald Schilderink, Matthew Bell, Eleonora Reginato, Chris Patten, Inmaculada Rioja, Francisca W Hilbers, Pawel A Kabala, Kris A Reedquist, David F Tough, Paul Peter Tak, Rab K Prinjha, Wouter J de Jonge
Transcription of inflammatory genes is tightly regulated by acetylation and deacetylation of histone tails. An inhibitor of the acetylated-lysine reader bromodomain and extra-terminal domain (BET) proteins, I-BET151, is known to counteract the induction of expression of inflammatory genes in macrophages. We have investigated the effects of I-BET151 on dendritic cell function, including expression of co-stimulatory molecules and cytokines, and capacity for T cell activation. Treatment of mouse bone marrow derived dendritic cells (BMDC) and human monocyte derived DCs (mdDC) with I-BET151 reduced LPS-induced expression of co-stimulatory molecules, as well as the production of multiple cyokines and chemokines...
November 2016: Molecular Immunology
https://www.readbyqxmd.com/read/27703987/immunomodulatory-effects-of-1-25-dihydroxyvitamin-d3-on-dendritic-cells-promote-induction-of-t-cell-hyporesponsiveness-to-myelin-derived-antigens
#14
Wai-Ping Lee, Barbara Willekens, Patrick Cras, Herman Goossens, Eva Martínez-Cáceres, Zwi N Berneman, Nathalie Cools
While emerging evidence indicates that dendritic cells (DC) play a central role in the pathogenesis of multiple sclerosis (MS), their modulation with immunoregulatory agents provides prospect as disease-modifying therapy. Our observations reveal that 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) treatment of monocyte-derived DC results in a semimature phenotype and anti-inflammatory cytokine profile as compared to conventional DC, in both healthy controls and MS patients. Importantly, 1,25(OH)2D3-treated DC induce T cell hyporesponsiveness, as demonstrated in an allogeneic mixed leukocyte reaction...
2016: Journal of Immunology Research
https://www.readbyqxmd.com/read/27697285/vitamin-d3-regulates-lamp3-expression-in-monocyte-derived-dendritic-cells
#15
L Malaguarnera, A Marsullo, K Zorena, G Musumeci, M Di Rosa
The family of lysosome-associated membrane proteins (LAMPs) encompassing LAMP1, LAMP2 and DC-LAMP (LAMP3) are the major constituents of the glycoconjugates coat present on the inside of the lysosomal membrane. LAMP3 is highly expressed only in certain cell types and during the differentiation stages. Its expression is linked the maturation of dendritic cells, inflammation, poor prognosis of certain tumors, and the locus where it is encoded was identified as a risk factor for Parkinson's disease (PD). Here, we investigated the capacity of Vitamin D3 to modulate the expression of LAMP3 during the dendritic cells differentiation and maturation...
January 2017: Cellular Immunology
https://www.readbyqxmd.com/read/27683749/il-10-modulated-human-dendritic-cells-for-clinical-use-identification-of-a-stable-and-migratory-subset-with-improved-tolerogenic-activity
#16
Fanny Kryczanowsky, Verena Raker, Edith Graulich, Matthias P Domogalla, Kerstin Steinbrink
Dendritic cells (DCs) are key regulators of protective immune responses and tolerance to (self-)Ags. Therefore, the scientific rationale for the use of tolerogenic DC therapy in the fields of allergies, autoimmunity, and transplantation medicine is strong. In this study, we analyzed the tolerogenic capacity of IL-10-modulated DC (IL-10DC) subpopulations to identify a DC subset that combines potent immunosuppressive activities with valuable immune properties for clinical implementation. IL-10DCs consist of two phenotypically distinct subpopulations: CD83(high)CCR7(+) IL-10DCs and CD83(low)CCR7(-) IL-10DCs...
September 28, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27667787/tolerogenic-dendritic-cells-generated-with-dexamethasone-and-vitamin-d3-regulate-rheumatoid-arthritis-cd4-t-cells-partly-via-transforming-growth-factor-%C3%AE-1
#17
A E Anderson, D J Swan, O Y Wong, M Buck, O Eltherington, R A Harry, A M Patterson, A G Pratt, G Reynolds, J-P Doran, J A Kirby, J D Isaacs, C M U Hilkens
Tolerogenic dendritic cells (tolDC) are a new immunotherapeutic tool for the treatment of rheumatoid arthritis (RA) and other autoimmune disorders. We have established a method to generate stable tolDC by pharmacological modulation of human monocyte-derived DC. These tolDC exert potent pro-tolerogenic actions on CD4(+) T cells. Lack of interleukin (IL)-12p70 production is a key immunoregulatory attribute of tolDC but does not explain their action fully. Here we show that tolDC express transforming growth factor (TGF)-β1 at both mRNA and protein levels, and that expression of this immunoregulatory cytokine is significantly higher in tolDC than in mature monocyte-derived DC...
January 2017: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/27658741/human-tolerogenic-dendritic-cells-generated-with-protein-kinase-c-inhibitor-are-optimal-for-functional-regulatory-t-cell-induction-a-comparative-study
#18
Endy Adnan, Takuya Matsumoto, Jun Ishizaki, Sachiko Onishi, Koichiro Suemori, Masaki Yasukawa, Hitoshi Hasegawa
Tolerogenic dendritic cells (tDCs) are a promising therapeutic tool for specific induction of immunological tolerance. Human tDCs can be generated ex vivo using various compounds. However, the compound(s) most suitable for clinical application remain undefined. We compared the tolerogenic properties of tDCs treated with protein kinase C inhibitor (PKCI), dexamethasone, vitamin D3 (Vit D3), rapamycin (Rapa), interleukin (IL)-10, transforming growth factor (TGF)-β, and a combination of peroxisome proliferator-activated receptor γ agonist and retinoic acid...
December 2016: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/27646959/tolerogenic-dendritic-cells
#19
REVIEW
Maisa C Takenaka, Francisco J Quintana
Deficits in immunological tolerance against self-antigens and antigens provided by the diet and commensal microbiota can result in the development of inflammatory and autoimmune disorders. Dendritic cells (DCs) are pivotal regulators of the immune response, specialized in antigen presentation to drive T cell priming and differentiation. DCs also have a tolerogenic function, participating in the enforcement of central and peripheral tolerance and the resolution of ongoing immune responses. Thus, DCs control effector and regulatory mechanisms relevant to the pathology of autoimmune disorders...
September 19, 2016: Seminars in Immunopathology
https://www.readbyqxmd.com/read/27634616/constitutively-active-stat5b-signaling-confers-tolerogenic-functions-to-dendritic-cells-of-nod-mice-and-halts-diabetes-progression
#20
Echarki Zerif, Aida Maalem, Simon Gaudreau, Chantal Guindi, Muhammad Ramzan, Steeve Véroneau, Denis Gris, Jana Stankova, Marek Rola-Pleszczynski, Walid Mourad, Gilles Dupuis, Abdelaziz Amrani
Defects in dendritic cells (DCs) development and function lead to autoimmune disorders. Autoimmune diabetes in humans and NOD mice results from a breakdown of self-tolerance, ending in T cell-mediated β-cell destruction. DCs dysfunction in NOD mice results in part from a defect in the JAK-STAT5 signaling pathway associated with the idd4 susceptibility locus. The involvement of Stat5b in DCs tolerogenic functions remains unknown. We have generated transgenic mice (NOD.CD11c(Stat5b-CA)) expressing a constitutively active form of the Stat5b gene (Stat5b-CA) under control of CD11c promoter...
January 2017: Journal of Autoimmunity
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