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Diabetes and dendritic cells

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https://www.readbyqxmd.com/read/29774025/co-stimulation-impaired-bone-marrow-derived-dendritic-cells-prevent-dextran-sodium-sulfate-induced-colitis-in-mice
#1
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
https://www.readbyqxmd.com/read/29760702/emerging-concepts-in-immune-thrombocytopenia
#2
REVIEW
Maurice Swinkels, Maaike Rijkers, Jan Voorberg, Gestur Vidarsson, Frank W G Leebeek, A J Gerard Jansen
Immune thrombocytopenia (ITP) is an autoimmune disease defined by low platelet counts which presents with an increased bleeding risk. Several genetic risk factors (e.g., polymorphisms in immunity-related genes) predispose to ITP. Autoantibodies and cytotoxic CD8+ T cells (Tc) mediate the anti-platelet response leading to thrombocytopenia. Both effector arms enhance platelet clearance through phagocytosis by splenic macrophages or dendritic cells and by induction of apoptosis. Meanwhile, platelet production is inhibited by CD8+ Tc targeting megakaryocytes in the bone marrow...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29754432/bim-determines-the-number-of-merocytic-dendritic-cells-a-cell-type-that-breaks-immune-tolerance
#3
Cindy Audiger, Sylvie Lesage
In contrast to conventional dendritic cells (cDC), when merocytic dendritic cells (mcDC) present antigens derived from apoptotic bodies, T cell anergy is reversed rather than induced, a process that promotes autoimmunity. Interestingly, mcDC are present in higher proportion in type 1 diabetes-prone NOD mice than in autoimmune-resistant B6 and BALB/c mice, and the Insulin-dependent diabetes 13 locus is linked to mcDC proportion. Therefore, mcDC are notably associated with susceptibility to autoimmune diabetes...
May 13, 2018: Immunology and Cell Biology
https://www.readbyqxmd.com/read/29752280/-drosophila-insulin-receptor-regulates-the-persistence-of-injury-induced-nociceptive-sensitization
#4
Seol Hee Im, Atit A Patel, Daniel N Cox, Michael J Galko
Diabetes-associated nociceptive hypersensitivity affects diabetic patients with hard-to-treat chronic pain. Because multiple tissues are affected by systemic alterations in insulin signaling, the functional locus of insulin signaling in diabetes-associated hypersensitivity remains obscure. Here, we used Drosophila nociception/nociceptive sensitization assays to investigate the role of Insulin receptor (Insulin-like receptor, InR) in nociceptive hypersensitivity. InR mutant larvae exhibited mostly normal baseline thermal nociception (absence of injury) and normal acute thermal hypersensitivity following UV-induced injury...
May 10, 2018: Disease Models & Mechanisms
https://www.readbyqxmd.com/read/29729445/emerging-role-of-il-35-in-inflammatory-autoimmune-diseases
#5
REVIEW
Lin-Chong Su, Xiao-Yan Liu, An-Fang Huang, Wang-Dong Xu
Interleukin 35 (IL-35) is the recently identified member of the IL-12 family of cytokines and provides the possibility to be a target for new therapies for autoimmune, inflammatory diseases. It is composed of an α chain (p35) and a β chain (EBI3). IL-35 mediates signaling by binding to its receptors, activates subsequent signaling pathways, and therefore, regulates the differentiation, function of T, B cells, macrophages, dendritic cells. Recent findings have shown abnormal expression of IL-35 in inflammatory autoimmune diseases, such as systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, multiple sclerosis, type 1 diabetes, psoriasis, multiple sclerosis, autoimmune hepatitis, experimental autoimmune uveitis...
May 3, 2018: Autoimmunity Reviews
https://www.readbyqxmd.com/read/29707204/loss-of-zbtb32-in-nod-mice-does-not-significantly-alter-t-cell-responses
#6
William D Coley, Yongge Zhao, Charles J Benck, Yi Liu, Chie Hotta-Iwamura, M Jubayer Rahman, Kristin V Tarbell
Background : We previously identified the transcriptional regulator Zbtb32 as a factor that can promote T cell tolerance in the Non-Obese Diabetic (NOD) mouse, a model of Type 1 diabetes. Antigen targeted to DCIR2 + dendritic cells (DCs) in vivo inhibited both diabetes and effector T cell expansion in NOD mice. Furthermore, Zbtb32 was preferentially induced in autoreactive CD4 T cells stimulated by these tolerogenic DCIR2 + DCs, and overexpression of Zbtb32 in islet-specific T cells inhibited the diabetes development by limiting T cell proliferation and cytokine production...
2018: F1000Research
https://www.readbyqxmd.com/read/29651443/immature-dendritic-cell-therapy-confers-durable-immune-modulation-in-an-antigen-dependent-and-antigen-independent-manner-in-nonobese-diabetic-mice
#7
Jeannette Lo, Chang-Qing Xia, Ruihua Peng, Michael J Clare-Salzler
Dendritic cell (DC) immunotherapy has been effective for prevention of type 1 diabetes (T1D) in NOD mice but fails to protect if initiated after active autoimmunity. As autoreactivity expands inter- and intramolecularly during disease progression, we investigated whether DCs unpulsed or pulsed with β cell antigenic dominant determinants (DD), subdominant determinants (SD), and ignored determinants (ID) could prevent T1D in mice with advanced insulitis. We found that diabetes was significantly delayed by DC therapy...
2018: Journal of Immunology Research
https://www.readbyqxmd.com/read/29599667/langerhans-cell-histiocytosis-in-children-a-disease-with-many-faces-recent-advances-in-pathogenesis-diagnostic-examinations-and-treatment
#8
REVIEW
Michalina Jezierska, Joanna Stefanowicz, Grzegorz Romanowicz, Wojciech Kosiak, Magdalena Lange
Langerhans cell histiocytosis is a rare clonal disease characterized by the proliferation of CD1a-positive immature dendritic cells. The purpose of this article was to present an updated review of recent advances in the pathogenesis, clinical features, imaging and treatment of this disease. The discovery of oncogenic BRAF mutations and the presence of proinflammatory cytokines and chemokines confirmed the unusual characteristics of this disease. Currently, children with organ involvement who do not have a good response to chemotherapy and have neurodegeneration or diabetes insipidus are the most problematic patients...
February 2018: Postȩpy Dermatologii i Alergologii
https://www.readbyqxmd.com/read/29578525/characterization-of-immune-cells-in-human-adipose-tissue-by-using-flow-cytometry
#9
Suzan Wetzels, Mitchell Bijnen, Erwin Wijnands, Erik A L Biessen, Casper G Schalkwijk, Kristiaan Wouters
Infiltration of immune cells in the subcutaneous and visceral adipose tissue (AT) deposits leads to a low-grade inflammation contributing to the development of obesity-associated complications such as type 2 diabetes. To quantitatively and qualitatively investigate the immune cell subsets in human AT deposits, we have developed a flow cytometry approach. The stromal vascular fraction (SVF), containing the immune cells, is isolated from subcutaneous and visceral AT biopsies by collagenase digestion. Adipocytes are removed after centrifugation...
March 6, 2018: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/29546475/targeted-delivery-of-antigen-to-intestinal-dendritic-cells-induces-oral-tolerance-and-prevents-autoimmune-diabetes-in-nod-mice
#10
Yulin Chen, Jie Wu, Jiajia Wang, Wenjing Zhang, Bohui Xu, Xiaojun Xu, Li Zong
AIMS/HYPOTHESIS: The intestinal immune system is an ideal target to induce immune tolerance physiologically. However, the efficiency of oral protein antigen delivery is limited by degradation of the antigen in the gastrointestinal tract and poor uptake by antigen-presenting cells. Gut dendritic cells (DCs) are professional antigen-presenting cells that are prone to inducing antigen-specific immune tolerance. In this study, we delivered the antigen heat shock protein 65-6×P277 (H6P) directly to the gut DCs of NOD mice through oral vaccination with H6P-loaded targeting nanoparticles (NPs), and investigated the ability of this antigen to induce immune tolerance to prevent autoimmune diabetes in NOD mice...
March 15, 2018: Diabetologia
https://www.readbyqxmd.com/read/29530798/depletion-of-dendritic-cells-in-perivascular-adipose-tissue-improves-arterial-relaxation-responses-in-type-2-diabetic-mice
#11
Tianyi Qiu, Min Li, Miles A Tanner, Yan Yang, James R Sowers, Ronald J Korthuis, Michael A Hill
BACKGROUND: Accumulation of multiple subtypes of immune cells in perivascular adipose tissue (PVAT) has been proposed to cause vascular inflammation and dysfunction in type 2 diabetes (T2DM). This study was designed to investigate specific roles for dendritic cells in PVAT in the development of vascular inflammation and impaired PVAT-mediated vasorelaxation in T2DM. METHODS AND RESULTS: Studies were performed using db/db mice (model of T2DM) and their Db heterozygote (DbHET), lean and normoglycemic controls...
March 9, 2018: Metabolism: Clinical and Experimental
https://www.readbyqxmd.com/read/29522531/differential-role-of-myd88-and-trif-signaling-in-myeloid-cells-in-the-pathogenesis-of-autoimmune-diabetes
#12
Ariadne Androulidaki, Laurens Wachsmuth, Apostolos Polykratis, Manolis Pasparakis
Type 1 diabetes (T1D) is caused by the autoimmune destruction of the insulin-producing pancreatic beta cells. While the role of adaptive immunity has been extensively studied, the role of innate immune responses and particularly of Toll- like Receptor (TLR) signaling in T1D remains poorly understood. Here we show that myeloid cell-specific MyD88 deficiency considerably protected mice from the development of streptozotocin (STZ)-induced diabetes. The protective effect of MyD88 deficiency correlated with increased expression of the immunoregulatory enzyme indoleamine 2,3-dioxygenase (IDO) in pancreatic lymph nodes from STZ-treated mice and in bone marrow-derived dendritic cells (BMDC) stimulated with apoptotic cells...
2018: PloS One
https://www.readbyqxmd.com/read/29497108/human-milk-oligosaccharides-protect-against-the-development-of-autoimmune-diabetes-in-nod-mice
#13
Ling Xiao, Belinda Van't Land, Phillip A Engen, Ankur Naqib, Stefan J Green, Angie Nato, Thea Leusink-Muis, Johan Garssen, Ali Keshavarzian, Bernd Stahl, Gert Folkerts
Development of Type 1 diabetes (T1D) is influenced by non-genetic factors, such as optimal microbiome development during early life that "programs" the immune system. Exclusive and prolonged breastfeeding is an independent protective factor against the development of T1D, likely via bioactive components. Human Milk Oligosaccharides (HMOS) are microbiota modulators, known to regulate immune responses directly. Here we show that early life provision (only for a period of six weeks) of 1% authentic HMOS (consisting of both long-chain, as well as short-chain structures), delayed and suppressed T1D development in non-obese diabetic mice and reduced development of severe pancreatic insulitis in later life...
March 1, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29491866/phosphatidylserine-liposomes-promote-tolerogenic-features-on-dendritic-cells-in-human-type-1-diabetes-by-apoptotic-mimicry
#14
Silvia Rodriguez-Fernandez, Irma Pujol-Autonell, Ferran Brianso, David Perna-Barrull, Mary Cano-Sarabia, Sonia Garcia-Jimeno, Adrian Villalba, Alex Sanchez, Eva Aguilera, Federico Vazquez, Joan Verdaguer, Daniel Maspoch, Marta Vives-Pi
Type 1 diabetes (T1D) is a metabolic disease caused by the autoimmune destruction of insulin-producing β-cells. With its incidence increasing worldwide, to find a safe approach to permanently cease autoimmunity and allow β-cell recovery has become vital. Relying on the inherent ability of apoptotic cells to induce immunological tolerance, we demonstrated that liposomes mimicking apoptotic β-cells arrested autoimmunity to β-cells and prevented experimental T1D through tolerogenic dendritic cell (DC) generation...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29482037/biology-and-function-of-adipose-tissue-macrophages-dendritic-cells-and-b-cells
#15
REVIEW
Stoyan Ivanov, Johanna Merlin, Man Kit Sam Lee, Andrew J Murphy, Rodolphe R Guinamard
The increasing incidence of obesity and its socio-economical impact is a global health issue due to its associated co-morbidities, namely diabetes and cardiovascular disease [1-5]. Obesity is characterized by an increase in adipose tissue, which promotes the recruitment of immune cells resulting in low-grade inflammation and dysfunctional metabolism. Macrophages are the most abundant immune cells in the adipose tissue of mice and humans. The adipose tissue also contains other myeloid cells (dendritic cells (DC) and neutrophils) and to a lesser extent lymphocyte populations, including T cells, B cells, Natural Killer (NK) and Natural Killer T (NKT) cells...
April 2018: Atherosclerosis
https://www.readbyqxmd.com/read/29478771/lipid-droplets-as-immune-modulators-in-myeloid-cells
#16
REVIEW
Martijn H den Brok, Tonke K Raaijmakers, Estel Collado-Camps, Gosse J Adema
Lipid droplets (LDs) were initially described as fat storage organelles in adipocytes, but are increasingly recognized as dynamic players in lipid metabolism, with important roles not only in diseases such as diabetes and cancer, but also in immune regulation. Alterations in immune cell function, such as myeloid cell activation, are connected to profound changes in LD numbers and LD protein composition. Thus, these organelles appear to be essential to metabolically support immune responses, and have a vital role in antigen crosspresentation, interferon (IFN) responses, production of inflammatory mediators, and pathogen clearance...
May 2018: Trends in Immunology
https://www.readbyqxmd.com/read/29468064/the-multiple-faces-of-langerhans-cell-histiocytosis-in-childhood-a-gentle-reminder
#17
Maria Papadopoulou, Paraskevi Panagopoulou, Anastasia Papadopoulou, Emmanuel Hatzipantelis, Ioannis Efstratiou, Assimina Galli-Tsinopoulou, Efimia Papadopoulou-Alataki
Langerhans cell histiocytosis (LCH) is a rare hematologic disorder that results from the clonal multiplication and accumulation of immature dendritic Langerhans cells. Its reported incidence rate varies, but is considered to be 2.6-8.9 per million children who are <15 years of age each year. It may affect any system or organ. The present study reported 4 pediatric LCH cases in order to highlight the heterogeneity of the initial presentation, and the pitfalls that may mislead clinicians and delay diagnosis...
March 2018: Molecular and Clinical Oncology
https://www.readbyqxmd.com/read/29463744/mhc-mismatched-mixed-chimerism-restores-peripheral-tolerance-of-noncross-reactive-autoreactive-t-cells-in-nod-mice
#18
Mingfeng Zhang, Jeremy J Racine, Qing Lin, Yuqing Liu, Shanshan Tang, Qi Qin, Tong Qi, Arthur D Riggs, Defu Zeng
Autoimmune type 1 diabetes (T1D) and other autoimmune diseases are associated with particular MHC haplotypes and expansion of autoreactive T cells. Induction of MHC-mismatched but not -matched mixed chimerism by hematopoietic cell transplantation effectively reverses autoimmunity in diabetic nonobese diabetic (NOD) mice, even those with established diabetes. As expected, MHC-mismatched mixed chimerism mediates deletion in the thymus of host-type autoreactive T cells that have T-cell receptor (TCR) recognizing (cross-reacting with) donor-type antigen presenting cells (APCs), which have come to reside in the thymus...
March 6, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29459428/attenuation-of-nk-cells-facilitates-mammary-tumor-growth-in-streptozotocin-induced-diabetes-in-mice
#19
Nevena Gajovic, Milena Jurisevic, Jelena Pantic, Gordana Radosavljevic, Nebojsa Arsenijevic, Miodrag L Lukic, Ivan Jovanovic
Diabetic patients have higher incidence and mortality of cancer. Recent study revealed that hyperglycemia-induced oxidative stress is involved in the acceleration of tumor metastasis. We used model of high-dose streptozotocin-induced diabetes to investigate its effect on tumor growth and modulation of antitumor immune response of 4T1 murine breast cancer in BALB/c mice. Diabetes accelerated tumor appearance, growth and weight, which was associated with decreased NK cells cytotoxicity against 4T1 tumor cells in vitro Diabetes reduced frequencies of systemic NKG2D+ , perforin+ , granzyme+ , IFN-γ+ and IL-17+ NK cells, while increased level of PD-1 expression and production of IL-10 in NK cells...
April 2018: Endocrine-related Cancer
https://www.readbyqxmd.com/read/29446740/role-of-immune-cells-in-diabetic-kidney-disease
#20
Xiaoqian Yang, Shan Mou
Diabetic Kidney Disease (DKD) is one of the major complications of Diabetes Mellitus (DM) and is currently the most common cause of End-Stage Renal Disease (ESRD) worldwide. Traditionally, DKD is considered a disease which has nothing to do with the immune system, and the pathogenesis is mainly characterized to be metabolic disturbance. Recent growing evidence indicates immunologic and inflammatory mechanisms in the development and progression of DKD. This overview of macrophages, dendritic cells, T lymphocytes, B lymphocytes, neutrophils and mast cells is closely involved in the pathologic process of DKD, with more emphasis on the leucocyte accumulation and related molecular mechanisms...
2017: Current Gene Therapy
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