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tolerogenic dc

Johannes Nowatzky, Olivier Manches, Shaukat Ali Khan, Emmanuelle Godefroy, Nina Bhardwaj
OBJECTIVE: Apoptotic cell receptors contribute to the induction of tolerance by modulating dendritic cell function following the uptake of apoptotic cells or microparticles. Dendritic cells that have bound or ingested apoptotic cells produce only low amounts of pro-inflammatory cytokines and fail to prime effector T cell responses. Specifically, ligation of the apoptotic cell receptor CR3 (CD11 b/CD18) on human monocyte-derived dendritic cells (moDC) down-modates proinflammatory cytokine secretion, but the consequences for human Th17 cell homeostasis and effector responses remain unknown...
June 13, 2018: Journal of Autoimmunity
Georgina Flórez-Grau, Irati Zubizarreta, Raquel Cabezón, Pablo Villoslada, Daniel Benitez-Ribas
The identification of activated T-lymphocytes restricted to myelin-derived immunogenic peptides in multiple sclerosis (MS) and aquaporin-4 water channel in neuromyelitis optica (NMO) in the blood of patients opened the possibility for developing highly selective and disease-specific therapeutic approaches. Antigen presenting cells and in particular dendritic cells (DCs) represent a strategy to inhibit pro-inflammatory T helper cells. DCs are located in peripheral and lymphoid tissues and are essential for homeostasis of T cell-dependent immune responses...
2018: Frontiers in Immunology
N Dobrovolskienė, V Pašukonienė, A Darinskas, J A Kraśko, K Žilionytė, A Mlynska, Ž Gudlevičienė, E Mišeikytė-Kaubrienė, V Schijns, W Lubitz, P Kudela, M Strioga
Cancer immunotherapy with dendritic cell (DC)-based vaccines has been used to treat various malignancies for more than two decades, however generally showed a limited clinical success. Among various factors responsible for their modest clinical activity is the lack of universally applied, standardized protocols for the generation of clinical-grade DC vaccines, capable of inducing effective anti-tumor immune responses. We investigated Bacterial Ghosts (BGs) - empty envelopes of Gram-negative bacteria - as a tool for optimized production of DC vaccines...
June 9, 2018: Vaccine
Mai Ohba, Kazuko Saeki, Tomoaki Koga, Toshiaki Okuno, Yuichi Kobayashi, Takehiko Yokomizo
Lipids are an energy source and key components of the cell membrane; however, they are also bioactive mediators of physiological and pathophysiological phenomena. Quantification of bioactive lipids is not easy because they have diverse chemical properties and are present in trace amounts. Here, we improved a multiplex method of quantifying bioactive lipids, thereby enabling measurement of 90 compounds simultaneously. We then used this system to quantify bioactive lipids produced by two subsets of dendritic cells (DCs): all-trans retinoic acid-treated DCs (RA-DCs) (a type of tolerogenic DC (tDC)) and conventional DCs (cDCs)...
June 8, 2018: Biochemical and Biophysical Research Communications
Laurence Pellerin, Ping Chen, Silvia Gregori, Gabriela Hernandez-Hoyos, Rosa Bacchetta, Maria Grazia Roncarolo
IL-10 is a potent immunosuppressive cytokine that promotes the differentiation of tolerogenic dendritic cells (DC-10), and the subsequent induction of antigen-specific T regulatory type 1 (Tr1) cells, which suppress immune responses. However, IL-10 acts on multiple cell types and its effects are not solely inhibitory, therefore, limiting its use as immunomodulant. APVO210 is a bispecific fusion protein composed of an anti-CD86 antibody fused with monomeric IL-10 (ADAPTIR™ from Aptevo Therapeutics). APVO210 specifically induces IL-10R signaling in CD86+ antigen-presenting cells, but not in T and B cells...
2018: Frontiers in Immunology
Ramya Sivakumar, Georges Abboud, Clayton E Mathews, Mark A Atkinson, Laurence Morel
The genetic analysis of the lupus-prone NZM2410 mouse has identified a suppressor locus, Sle2c2 , which confers resistance to spontaneous lupus in combination with NZM2410 susceptibility loci, or in the chronic graft-versus-host disease (cGVHD) induced model of lupus in the B6. Sle2c2 congenic strain. The candidate gene for  Sle2c2 , the Csf3r gene encoding the granulocyte colony-stimulating factor receptor (G-CSF-R/CD114), was validated when cGVHD was restored in B6. Sle2c2 mice after treatment with G-CSF...
2018: Frontiers in Immunology
Faye A H Cooles, Amy E Anderson, Andrew Skelton, Arthur G Pratt, Mariola S Kurowska-Stolarska, Iain McInnes, Catharien M U Hilkens, John D Isaacs
Objective: Dendritic cells (DCs) are key orchestrators of immune function. To date, rheumatoid arthritis (RA) researchers have predominantly focused on a potential pathogenic role for CD1c+ DCs. In contrast, CD141+ DCs and plasmacytoid DCs (pDCs) have not been systematically examined, at least in early RA. In established RA, the role of pDCs is ambiguous and, since disease duration and treatment both impact RA pathophysiology, we examined pDCs, and CD1c+ and CD141+ conventional DCs (cDCs), in early, drug-naïve RA (eRA) patients...
2018: Frontiers in Immunology
Hsi-Ju Wei, John J Letterio, Tej K Pareek
The immune system operates by maintaining a tight balance between coordinating responses against foreign antigens and maintaining an unresponsive state against self-antigens as well as antigens derived from commensal organisms. The disruption of this immune homeostasis can lead to chronic inflammation and to the development of autoimmunity. Dendritic cells (DCs) are the professional antigen-presenting cells of the innate immune system involved in activating naïve T cells to initiate immune responses against foreign antigens...
May 18, 2018: Journal of Visualized Experiments: JoVE
Charles R Schutt, Howard E Gendelman, R Lee Mosley
BACKGROUND: Administration of granulocyte-macrophage colony-stimulating factor (GM-CSF) increases regulatory T cell (Treg) number and function with control of neuroinflammation and neuronal protection in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model of Parkinson's disease (PD). Recently, we demonstrated in an early phase 1 clinical trial that GM-CSF also improves motor skills in PD patients. However, the mechanisms of Treg induction and its effects on neuroprotective responses remain unknown...
May 21, 2018: Molecular Neurodegeneration
Carl Engman, Yesica Garciafigueroa, Brett Eugene Phillips, Massimo Trucco, Nick Giannoukakis
Dendritic cells (DC) are important in the onset and severity of inflammatory bowel disease (IBD). Tolerogenic DC induce T-cells to become therapeutic Foxp3+ regulatory T-cells (Tregs). We therefore asked if experimental IBD could be prevented by administration of bone marrow-derived DC generated under conventional GM-CSF/IL-4 conditions but in the presence of a mixture of antisense DNA oligonucleotides targeting the primary transcripts of CD40, CD80, and CD86. These cell products (which we call AS-ODN BM-DC) have demonstrated tolerogenic activity in preventing type 1 diabetes and preserving beta cell mass in new-onset type 1 diabetes in the NOD mouse strain, in earlier studies...
2018: Frontiers in Immunology
Inmaculada Serrano, Ana Luque, Josep M Aran
The acute phase response is generated by an overwhelming immune-inflammatory process against infection or tissue damage, and represents the initial response of the organism in an attempt to return to homeostasis. It is mediated by acute phase proteins (APPs), an assortment of highly conserved plasma reactants of seemingly different functions that, however, share a common protective role from injury. Recent studies have suggested a crosstalk between several APPs and the mononuclear phagocyte system (MPS) in the resolution of inflammation, to restore tissue integrity and function...
2018: Frontiers in Immunology
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
M Berings, P Gevaert, N De Ruyck, L Derycke, G Holtappels, C Pilette, C Bachert, B N Lambrecht, M Dullaers
BACKGROUND: In humans, both basophils and dendritic cells (DCs) express the high-affinity IgE receptor (FcεRI). OBJECTIVE: To gain more insight into the relation between serum IgE levels and FcεRI expression and IgE binding by DCs and basophils in house dust mite (HDM) allergy and during subcutaneous immunotherapy (SCIT). METHODS: We measured FcεRI, IgE and HDM allergen on DCs (conventional type 2 DCs, cDC2s; plasmacytoid dendritic cells, pDCs) and basophils by flow cytometry in 22 non-allergic vs 52 allergic subjects and upon HDM SCIT in 28 allergic subjects...
April 22, 2018: Clinical and Experimental Allergy: Journal of the British Society for Allergy and Clinical Immunology
Sim L Tung, Dominic A Boardman, Monica Sen, Marilena Letizia, Qi Peng, Nicole Cianci, Laura Dioni, Leo M Carlin, Robert Lechler, Valentina Bollati, Giovanna Lombardi, Lesley A Smyth
Regulatory T cells (Treg) are a subpopulation of T cells that maintain tolerance to self and limit other immune responses. They achieve this through different mechanisms including the release of extracellular vesicles (EVs) such as exosomes as shown by us, and others. One of the ways that Treg derived EVs inhibit target cells such as effector T cells is via the transfer of miRNA. Another key target for the immunoregulatory function of Tregs is the dendritic cells (DCs). In this study we demonstrate directly, and for the first time, that miRNAs are transferred from Tregs to DCs via Treg derived EVs...
April 17, 2018: Scientific Reports
Jae-Il Lee, Hi-Jung Park, Hye-Jin Park, Yun-Jung Choi, Jiyeon Kim, Jin Kyun Park, Kyeong Cheon Jung, Eung-Soo Hwang, Eun Bong Lee, Seong Hoe Park
Identification of a particular epitope on the domain 2 of human ICAM-1 led us to focus on its role in the treatment of rheumatoid arthritis (RA). Key observations from our previous xenotransplantation research included the generation of tolerogenic DCs, antigen-specific T-cell tolerance, and reduced production of inflammatory cytokines. The critically important point is the fact that it works initially on DC maturation. Ligation of this epitope with a recognizing antibody, MD-3, was also able to create a tolerogenic environment in RA in a manner sililar to that created by xenotransplantation...
June 2, 2018: Biochemical and Biophysical Research Communications
Thomas K Hoang, Baokun He, Ting Wang, Dat Q Tran, Jon Marc Rhoads, Yuying Liu
Lactobacillus reuteri DSM 17938 (LR 17938) has been shown to reduce the incidence and severity of necrotizing enterocolitis (NEC). It is unclear if preventing NEC by LR 17938 is mediated by toll-like receptor 2 (TLR2), which is known to mediate pro-inflammatory responses to bacterial cell wall components. NEC was induced in newborn TLR2-/- or WT mice by the combination of gavage-feeding cow milk-based formula and exposure to hypoxia and cold stress. Treatment groups were administered formula supplemented with LR 17938 or placebo (MRS media)...
April 12, 2018: American Journal of Physiology. Gastrointestinal and Liver Physiology
Stefan Schülke
Dendritic cells (DCs) are gatekeepers of the immune system that control induction and polarization of primary, antigen-specific immune responses. Depending on their maturation/activation status, the molecules expressed on their surface, and the cytokines produced DCs have been shown to either elicit immune responses through activation of effector T cells or induce tolerance through induction of either T cell anergy, regulatory T cells, or production of regulatory cytokines. Among the cytokines produced by tolerogenic DCs, interleukin 10 (IL-10) is a key regulatory cytokine limiting und ultimately terminating excessive T-cell responses to microbial pathogens to prevent chronic inflammation and tissue damage...
2018: Frontiers in Immunology
Ghita Ghislat, Toby Lawrence
Autophagy and immunity share the property of being auto-protective for the organism. Autophagy is an important degradation pathway that buffers nutrient deprivation by recycling macromolecules in organisms from yeast to man. Perturbations in autophagy are associated with inflammation and cancer development. Emerging studies have characterized the molecular details regarding how autophagy is controlled by immune cells. Among these, dendritic cells (DCs) are one of the most potent professional antigen-presenting cells critical for the activation of naïve T cells to maintain immune tolerance and drive protective immunity to infection and cancer...
March 26, 2018: Cellular & Molecular Immunology
Taylor T Chrisikos, Yifan Zhou, Natalie Slone, Rachel Babcock, Stephanie S Watowich, Haiyan S Li
Dendritic cells (DCs) are the principal antigen-presenting cells of the immune system and play key roles in controlling immune tolerance and activation. As such, DCs are chief mediators of tumor immunity. DCs can regulate tolerogenic immune responses that facilitate unchecked tumor growth. Importantly, however, DCs also mediate immune-stimulatory activity that restrains tumor progression. For instance, emerging evidence indicates the cDC1 subset has important functions in delivering tumor antigens to lymph nodes and inducing antigen-specific lymphocyte responses to tumors...
March 14, 2018: Molecular Immunology
Emilia Vendelova, Diyaaeldin Ashour, Patrick Blank, Florian Erhard, Antoine-Emmanuel Saliba, Ulrich Kalinke, Manfred B Lutz
Dendritic cells (DCs) are key directors of tolerogenic and immunogenic immune responses. During the steady state, DCs maintain T cell tolerance to self-antigens by multiple mechanisms including inducing anergy, deletion, and Treg activity. All of these mechanisms help to prevent autoimmune diseases or other hyperreactivities. Different DC subsets contribute to pathogen recognition by expression of different subsets of pattern recognition receptors, including Toll-like receptors or C-type lectins. In addition to the triggering of immune responses in infected hosts, most pathogens have evolved mechanisms for evasion of targeted responses...
2018: Frontiers in Immunology
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