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tolerogenic dc

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https://www.readbyqxmd.com/read/28978469/prostaglandin-e2-leads-to-the-acquisition-of-dnmt3a-dependent-tolerogenic-functions-in-human-myeloid-derived-suppressor-cells
#1
Javier Rodríguez-Ubreva, Francesc Català-Moll, Nataša Obermajer, Damiana Álvarez-Errico, Ricardo N Ramirez, Carlos Company, Roser Vento-Tormo, Gema Moreno-Bueno, Robert P Edwards, Ali Mortazavi, Pawel Kalinski, Esteban Ballestar
Myeloid-derived suppressor cells (MDSCs) and dendritic cells (DCs) arise from common progenitors. Tumor-derived factors redirect differentiation from immune-promoting DCs to tolerogenic MDSCs, an immunological hallmark of cancer. Indeed, in vitro differentiation of DCs from human primary monocytes results in the generation of MDSCs under tumor-associated conditions (PGE2 or tumor cell-conditioned media). Comparison of MDSC and DC DNA methylomes now reveals extensive demethylation with specific gains of DNA methylation and repression of immunogenic-associated genes occurring in MDSCs specifically, concomitant with increased DNA methyltransferase 3A (DNMT3A) levels...
October 3, 2017: Cell Reports
https://www.readbyqxmd.com/read/28960227/tolerogenic-dendritic-cells-induced-by-bd750-ameliorate-proinflammatory-t-cell-responses-and-experimental-autoimmune-encephalitis-in-mice
#2
Yan Zhou, Xiao Leng, Hua Li, Shuxia Yang, Tai Yang, Limei Li, Ying Xiong, Qiang Zou, Yang Liu, Yantang Wang
BD750, a novel JAK3/STAT5 inhibitor, can inhibit T cell proliferation. This study aims to evaluate whether BD750 can induce tolerogenic dendritic cells (tolDC) and their function in experimental autoimmune encephalitis (EAE) in mice. Following BD750 treatment, LPS-induced maturation of DC, allogeneic T cell proliferation, Th1 and Th17 cell functional differentiation, the STAT5 and AKT activation were determined. The effect of tolDC loaded with antigen peptide on the development and severity of EAE and their splenic Th1 and Th17 cell responses were determined...
September 27, 2017: Molecular Medicine
https://www.readbyqxmd.com/read/28946811/impaired-function-of-bone-marrow-mesenchymal-stem-cells-from-immune-thrombocytopenia-patients-in-inducing-regulatory-dc-differentiation-via-the-notch-1-jagged-1-signaling-pathway
#3
Linlin Xu, Haixia Fu, Jiamin Zhang, Feier Feng, Qianming Wang, Xiaolu Zhu, Jing Xue, Chencong Wang, Qi Chen, Xiao Liu, Yazhe Wang, Yazhen Qin, Yuan Kong, Yingjun Chang, Lanping Xu, Kaiyan Liu, Xiaojun Huang, Xiaohui Zhang
Immune thrombocytopenia (ITP) is an autoimmune disease in which dendritic cells (DCs) play a crucial role in the break-down of self-tolerance. Studies have identified the function of mesenchymal stem cells (MSCs) in promoting the development of regulatory DCs (regDCs). Our previous work revealed that MSCs in ITP exerted senescence, apoptosis and impaired immunosuppressive effects on T and B cells. However, it is unclear whether the effects of MSCs on regDC induction are altered in ITP. Our data demonstrated that MSCs in ITP were impaired in inhibiting CD1a+DC and CD14+DC differentiation from CD34+ hematopoietic progenitor cells (CD34+HPCs)...
September 25, 2017: Stem Cells and Development
https://www.readbyqxmd.com/read/28913556/high-dose-vitamin-d3-supplementation-decreases-the-number-of-colonic-cd103-dendritic-cells-in-healthy-subjects
#4
Nina Friis Bak, M Bendix, S Hald, L Reinert, M K Magnusson, J Agnholt
PURPOSE: Vitamin D may induce tolerance in the intestinal immune system and has been shown to regulate the phenotype of tolerogenic intestinal dendritic cells (DCs) in vitro. It is unknown whether vitamin D supplementation affects human intestinal DCs in vivo, and we aimed to investigate the tolerability and effect on intestinal CD103(+)DCs of high-dose vitamin D3 treatment in healthy subjects. METHODS: Ten healthy subjects received a total of 480,000 IU oral vitamin D3 over 15 days and colonic biopsies were obtained before and after intervention by endoscopy...
September 14, 2017: European Journal of Nutrition
https://www.readbyqxmd.com/read/28906131/effects-of-immunomodulators-on-the-response-induced-by-vaccines-against-autoimmune-diseases
#5
Dante J Marciani
A promising treatment for T-cell-mediated autoimmune diseases is the induction of immune tolerance by modulating the immune response against self-antigens, an objective that may be achieved by vaccination. There are two main types of vaccines currently under development. The tolerogenic vaccines, composed of proteins formed by a cytokine fused to a self-antigen, which usually induce tolerance by eliminating the T-cells that are immune reactive against the self-antigen. The immunogenic vaccines, comprised of a self-antigen plus a sole Th2 adjuvant either free or conjugated, that alleviate autoimmunity by switching the immune response against the self-antigen, from a damaging pro-inflammatory Th1/Th17 to an anti-inflammatory Th2 immunity...
September 14, 2017: Autoimmunity
https://www.readbyqxmd.com/read/28901417/discrimination-of-the-heterogeneity-of-bone-marrow%C3%A2-derived-dendritic-cells
#6
Jing Wang, Xiaomin Dai, Chiaching Hsu, Changsheng Ming, Ying He, Ji Zhang, Lai Wei, Ping Zhou, Cong-Yi Wang, Jun Yang, Nianqiao Gong
The present study aimed to discriminate different subsets of cultured dendritic cells (DCs) to evaluate their immunological characteristics. DCs offer an important foundation for immunological studies, and mouse bone marrow (BM) cells cultured with granulocyte‑macrophage colony‑stimulating factor (GM‑CSF) have been used extensively to generate CD11c+/major histocompatibility complex II+ BM‑derived DCs (BMDCs). Immature DCs are considered to have strong migration and phagocytic antigen‑capturing abilities, whereas mature DCs are thought to activate naive T cells and express high levels of costimulatory cytokines and adhesion molecules...
September 8, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28900681/regulatory-dendritic-cells
#7
Katsuaki Sato, Tomofumi Uto, Tomohiro Fukaya, Hideaki Takagi
Dendritic cells (DCs) comprise heterogeneous subsets, functionally classified into conventional DCs (cDCs) and plasmacytoid DCs (pDCs). DCs are considered to be essential antigen (Ag)-presenting cells (APCs) that play crucial roles in activation and fine-tuning of innate and adaptive immunity under inflammatory conditions, as well as induction of immune tolerance to maintain immune homeostasis under steady-state conditions. Furthermore, DC functions can be modified and influenced by stimulation with various extrinsic factors, such as ligands for pattern-recognition receptors (PRRs) and cytokines...
September 13, 2017: Current Topics in Microbiology and Immunology
https://www.readbyqxmd.com/read/28892752/graphene-quantum-dots-suppress-proinflammatory-t-cell-responses-via-autophagy-dependent-induction-of-tolerogenic-dendritic-cells
#8
Sergej Tomić, Kristina Janjetović, Dušan Mihajlović, Marina Milenković, Tamara Kravić-Stevović, Zoran Marković, Biljana Todorović-Marković, Zdenko Spitalsky, Matej Micusik, Dragana Vučević, Miodrag Čolić, Vladimir Trajković
Graphene quantum dots (GQD) are atom-thick nanodimensional carbon sheets with excellent physico-chemical and biological properties, making them attractive for application in theranostics. However, their immunoregulatory properties are insufficiently investigated, especially in human primary immune cells. We found that non-toxic doses of GQD inhibit the production of proinflammatory and T helper (Th)1 cytokines, and augment the production of anti-inflammatory and Th2 cytokines by human peripheral blood mononuclear cells...
November 2017: Biomaterials
https://www.readbyqxmd.com/read/28851867/a-unique-tolerizing-dendritic-cell-phenotype-induced-by-the-synthetic-triterpenoid-cddo-dfpa-rta-408-is-protective-against-eae
#9
Hsi-Ju Wei, Tej K Pareek, Qi Liu, John J Letterio
Tolerogenic dendritic cells (DCs) have emerged as relevant clinical targets for the treatment of multiple sclerosis and other autoimmune disorders. However, the pathways essential for conferring the tolerizing DC phenotype and optimal methods for their induction remain an intense area of research. Triterpenoids are a class of small molecules with potent immunomodulatory activity linked to activation of Nrf2 target genes, and can also suppress the manifestations of experimental autoimmune encephalomyelitis (EAE)...
August 29, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28826942/dendritic-cells-as-inducers-of-peripheral-tolerance
#10
REVIEW
Courtney A Iberg, Andrew Jones, Daniel Hawiger
Mechanisms of tolerance initiated in the thymus are indispensable for establishing immune homeostasis, but they may not be sufficient to prevent tissue-specific autoimmune diseases. In the periphery, dendritic cells (DCs) play a crucial tolerogenic role, extending the maintenance of immune homeostasis and blocking autoimmune responses. We review here these essential roles of DCs in orchestrating mechanisms of peripheral T cell tolerance as determined by targeted delivery of defined antigens to DCs in vivo in combination with various genetic modifications of DCs...
August 18, 2017: Trends in Immunology
https://www.readbyqxmd.com/read/28754680/versican-derived-matrikines-regulate-batf3-dendritic-cell-differentiation-and-promote-t-cell-infiltration-in-colorectal-cancer
#11
Chelsea Hope, Philip B Emmerich, Athanasios Papadas, Adam Pagenkopf, Kristina A Matkowskyj, Dana R Van De Hey, Susan N Payne, Linda Clipson, Natalie S Callander, Peiman Hematti, Shigeki Miyamoto, Michael G Johnson, Dustin A Deming, Fotis Asimakopoulos
Colorectal cancer originates within immunologically complex microenvironments. To date, the benefits of immunotherapy have been modest, except in neoantigen-laden mismatch repair-deficient tumors. Approaches to enhance tumor-infiltrating lymphocytes in the tumor bed may substantially augment clinical immunotherapy responses. In this article, we report that proteolysis of the tolerogenic matrix proteoglycan versican (VCAN) strongly correlated with CD8(+) T cell infiltration in colorectal cancer, regardless of mismatch repair status...
September 1, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28723546/local-modulation-of-antigen-presenting-cell-development-after-resolution-of-pneumonia-induces-long-term-susceptibility-to-secondary-infections
#12
Antoine Roquilly, Hamish E G McWilliam, Cedric Jacqueline, Zehua Tian, Raphael Cinotti, Marie Rimbert, Linda Wakim, Irina Caminschi, Mireille H Lahoud, Gabrielle T Belz, Axel Kallies, Justine D Mintern, Karim Asehnoune, Jose A Villadangos
Lung infections cause prolonged immune alterations and elevated susceptibility to secondary pneumonia. We found that, after resolution of primary viral or bacterial pneumonia, dendritic cells (DC), and macrophages exhibited poor antigen-presentation capacity and secretion of immunogenic cytokines. Development of these "paralyzed" DCs and macrophages depended on the immunosuppressive microenvironment established upon resolution of primary infection, which involved regulatory T (Treg) cells and the cytokine TGF-β...
July 18, 2017: Immunity
https://www.readbyqxmd.com/read/28720647/in-situ-targeting-of-dendritic-cells-sets-tolerogenic-environment-and-ameliorates-cd4-t-cell-response-in-the-postischemic-liver
#13
Dominik Funken, Hellen Ishikawa-Ankerhold, Bernd Uhl, Maximilian Lerchenberger, Markus Rentsch, Doris Mayr, Steffen Massberg, Jens Werner, Andrej Khandoga
CD4(+) T cells recruited to the liver play a key role in the pathogenesis of ischemia/reperfusion (I/R) injury. The mechanism of their activation during alloantigen-independent I/R is not completely understood. We hypothesized that liver-resident dendritic cells (DCs) interact with CD4(+) T cells in the postischemic liver and that modulation of DCs or T-cell-DC interactions attenuates liver inflammation. In mice, warm hepatic I/R (90/120-240 min) was induced. Tolerogenic DCs were generated in situ by pretreatment of animals with the vitamin D analog paricalcitol...
July 18, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28689791/peanut-specific-tr1-cells-induced-in-vitro-from-allergic-individuals-are-functionally-impaired
#14
Laurence Pellerin, Jennifer Anne Jenks, Sharon Chinthrajah, Tina Dominguez, Whitney Block, Xiaoying Zhou, Arram Noshirvan, Silvia Gregori, Maria Grazia Roncarolo, Kari Christine Nadeau, Rosa Bacchetta
BACKGROUND: Peanut allergy is a life threatening condition which lacks regulatory-approved treatment. T regulatory type 1 (Tr1) cells are potent suppressors of immune responses and can be induced in vivo upon repeated antigen exposure or in vitro using tolerogenic dendritic cells (DC-10). Whether or not oral immunotherapy (OIT) leads to antigen-specific Tr1 cell induction has not been established. OBJECTIVES: To determine whether peanut-specific Tr1 cells can be generated in vitro from peripheral blood of peanut allergic (PA) individuals at baseline or during OIT, and whether they are functional as compared to peanut-specific Tr1 cells induced from healthy controls (HC)...
July 6, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28680757/downregulation-of-ptp1b-and-tc-ptp-phosphatases-potentiate-dendritic-cell-based-immunotherapy-through-il-12-ifn%C3%AE-signaling
#15
Claudia Penafuerte, Matthew Feldhammer, John R Mills, Valerie Vinette, Kelly A Pike, Anita Hall, Eva Migon, Gerard Karsenty, Jerry Pelletier, George Zogopoulos, Michel L Tremblay
PTP1B and TC-PTP are highly related protein-tyrosine phosphatases (PTPs) that regulate the JAK/STAT signaling cascade essential for cytokine-receptor activation in immune cells. Here, we describe a novel immunotherapy approach whereby monocyte-derived dendritic cell (moDC) function is enhanced by modulating the enzymatic activities of PTP1B and TC-PTP. To downregulate or delete the activity/expression of these PTPs, we generated mice with PTP-specific deletions in the dendritic cell compartment or used PTP1B and TC-PTP specific inhibitor...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28675711/modification-of-anti-tumor-immunity-by-tolerogenic-dendritic-cells
#16
Liying Chen, Mohammad Sharif Hasni, Mikael Jondal, Konstantin Yakimchuk
Immunosuppressive functions of glucocorticoids (GC) can be mediated via various mechanisms, including the modulation of dendritic cells (DC). Our study investigates the effects of tolerogenic GC-treated DCs on NK and T cell anti-tumor responses in OT-1/Rag(-/-) mice, expressing a transgenic TCR in CD8(+) T cells. The effects caused by GC-treated DCs were compared to the responses to immunogenic, CpG-activated DCs. The effects of DCs on anti-tumor immune responses were analyzed using the EG7 tumor model, where the tumor cells express the peptide epitope recognized by OT-1 T cells...
July 4, 2017: Autoimmunity
https://www.readbyqxmd.com/read/28673320/the-clinical-importance-of-tumour-infiltrating-macrophages-and-dendritic-cells-in-periampullary-adenocarcinoma-differs-by-morphological-subtype
#17
Sebastian Lundgren, Emelie Karnevi, Jacob Elebro, Björn Nodin, Mikael C I Karlsson, Jakob Eberhard, Karin Leandersson, Karin Jirström
BACKGROUND: Dendritic cells (DC) and tumour-associated macrophages (TAM) are essential in linking the innate and adaptive immune response against tumour cells and tumour progression. These cells are also potential target for immunotherapy as well as providing a handle to investigate immune status in the tumour microenvironment. The aim of the present study was to examine their impact on prognosis and chemotherapy response in periampullary adenocarcinoma, including pancreatic cancer, with particular reference to morphological subtype...
July 3, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28601056/eliciting-th1-immune-response-using-casein-alpha-s1-loaded-dendritic-cells
#18
Saeed Daneshmandi, Maryam Nourizadeh, Zahra Pourpak, Ali Akbar Pourfathollah
Allergen-specific immunotherapy (AIT) has been recently considered as an alternative approach to ameliorate the symptoms of allergen exposure and improvement the patients' quality of life. Dendritic cells (DC) in the forms of tolerogenic or Th1-induced cells have been investigated in several studies as one of the promising approaches of AIT in allergic diseases. The aim of this study was to evaluate the potency of casein-loaded DCs in eliciting the Th1 immune responses in Balb/c mice as a potential therapeutic approach in allergic condition...
April 2017: Iranian Journal of Allergy, Asthma, and Immunology
https://www.readbyqxmd.com/read/28594751/dhrs9-is-a-stable-marker-of-human-regulatory-macrophages
#19
Paloma Riquelme, Giada Amodio, Camila Macedo, Aurelie Moreau, Nataša Obermajer, Christoph Brochhausen, Norbert Ahrens, Tuija Kekarainen, Fred Fändrich, Cristina Cuturi, Silvia Gregori, Diana Metes, Hans J Schlitt, Angus W Thomson, Edward K Geissler, James A Hutchinson
BACKGROUND: The human regulatory macrophage (Mreg) has emerged as a promising cell type for use as a cell-based adjunct immunosuppressive therapy in solid organ transplant recipients. In this brief report, dehydrogenase/reductase 9 (DHRS9) is identified as a robust marker of human Mregs. MATERIALS AND METHODS: The cognate antigen of a mouse monoclonal antibody raised against human Mregs was identified as DHRS9 by immunoprecipitation and MALDI-MS sequencing. Expression of DHRS9 within a panel of monocyte-derived macrophages was investigated by quantitative PCR, immunoblotting and flow cytometry...
June 7, 2017: Transplantation
https://www.readbyqxmd.com/read/28579377/dendritic-cells-conditioned-by-activin-a-induced-regulatory-t-cells-exhibit-enhanced-tolerogenic-properties-and-protect-against-experimental-asthma
#20
Maria Semitekolou, Ioannis Morianos, Aggelos Banos, Dimitris Konstantopoulos, Marina Adamou-Tzani, Tim Sparwasser, Georgina Xanthou
BACKGROUND: Previously, we have demonstrated that regulatory T (Treg) cells, induced by the cytokine activin-A, suppress Th2-mediated allergic responses and linked airway disease. Still, the effects of activin-A-induced Treg cells (act-A-iTreg cells) on the regulation of dendritic cell (DC)-driven allergic inflammation remain elusive. OBJECTIVE: Here, we investigated whether act-A-iTreg cells can modulate DC responses and endow them with enhanced tolerogenic functions...
June 1, 2017: Journal of Allergy and Clinical Immunology
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