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Diabetes and dendritic cells

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
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
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
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
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...
February 20, 2018: Atherosclerosis
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...
February 22, 2018: Trends in Immunology
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
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...
February 20, 2018: Proceedings of the National Academy of Sciences of the United States of America
Nevena Gajovic, Milena Jurisevic, Jelena Pantic, Gordana D Radosavljevic, Nebojsa Arsenijevic, Miodrag 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...
February 19, 2018: Endocrine-related Cancer
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...
February 13, 2018: Current Gene Therapy
Maria Sambataro, Luisa Sambado, Enrica Trevisiol, Matilde Cacciatore, Anna Furlan, Piero Maria Stefani, Elena Seganfreddo, Elisabetta Durante, Stefania Conte, Silvia Della Bella, Agostino Paccagnella, Angelo Paolo Dei Tos
Diabetic neuropathy is the most common complication of diabetes and is frequently associated with foot ischemia and infection, but its pathogenesis is controversial. We hypothesized that proinsulin expression in peripheral blood mononuclear cells is a process relevant to this condition and could represent a link among hyperglycemia, nerve susceptibility, and diabetic foot lesions. We assessed proinsulin expression by using flow cytometry in dendritic cells from control participants and patients with type 2 diabetic with or without peripheral neuropathy or accompanied by diabetic foot...
February 12, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Tomasz Przybyła, Monika Sakowicz-Burkiewicz, Tadeusz Pawełczyk
Adenosine and adenosine triphosphate are involved in purinergic signaling which plays an important role in control of the immune system. Much data have been obtained regarding impact of purinergic signaling on dendritic cells, macrophages, monocytes and T lymphocytes, however less attention has been paid to purinergic regulation of B cells. This review summarizes present knowledge on ATP- and Ado-dependent signaling in B lymphocytes. Human B cells have been shown to express A1-AR, A2A-AR, A2B-AR and A3-AR and each subtype of P2 receptors...
January 23, 2018: Acta Biochimica Polonica
David Bernardo, María Chaparro, Javier P Gisbert
Inflammatory bowel disease (IBD), including Crohn's disease and ulcerative colitis, is a serious, costly and persistent health problem with an estimated prevalence in Western countries around 0.5% of the general population; its socioeconomic impact is comparable with that for chronic diseases such as diabetes. Conventional treatment involves escalating drug regimens with concomitant side effects followed, in some cases, by surgical interventions which are often multiple, mainly in Crohn's disease. The goal of finding a targeted gut-specific immunotherapy for IBD patients is therefore an important unmet need...
January 16, 2018: Molecular Nutrition & Food Research
K Kochet, I Lytus, I Svistunov, O Sulaieva
Skin pathology is registered in vast majority of patients with diabetes mellitus (DM). Despite the abundance of publications on dermatological problems in DM, there is still a number of gaps to be discussed in terms of pathophysiological mechanisms. The goal of this review was to assess the mechanisms of development of different skin pathologies under DM. One of the key pathogenic mechanisms of skin lesions in diabetes is hyperglycemia and the effects of the advanced glycation end products, inducing oxidative stress, endothelial dysfunction and inflammation; that in its turn can accelerate the mechanisms of skin aging, the development of diabetic dermopathy and scleredema diabeticorum...
December 2017: Georgian Medical News
Jaroslava Halper
Though the composition of the three layers constituting the blood vessel wall varies among the different types of blood vessels, and some layers may even be missing in capillaries, certain basic components, and properties are shared by all blood vessels, though each histologically distinct layer contains a unique complement of extracellular components, growth factors and cytokines, and cell types as well. The structure and composition of vessel layers informs and is informed by the function of the particular blood vessel...
2018: Advances in Pharmacology
Aziz Mahmoudzadeh, Ali Akbar Pourfathollah, Mohammad Hossein Karimi, Seyed Mohammad Moazzeni
BACKGROUND: Type-1 diabetes (T1D) is an autoimmune disease in which T lymphocytes destroy insulin-producing β-cells. Control of self-reactive T lymphocytes and recovery of diabetic injury is the end point of T1D. OBJECTIVE: To investigate generation of tolerogenic dendritic cells (tolDCs) as an innovative method of diabetes therapy. METHODS: Lentivirus vector production was achieved by GIPZ mouse CD40 shRNA, psPAX2 and pMD2G plasmids DNA...
December 2017: Iranian Journal of Immunology: IJI
Maria Teresa Ventura, Marco Casciaro, Sebastiano Gangemi, Rosalba Buquicchio
Background: The immunosenescence is a relatively recent chapter, correlated with the linear extension of the average life began in the nineteenth century and still in progress. The most important feature of immunosenescence is the accumulation in the "immunological space" of memory and effector cells as a result of the stimulation caused by repeated clinical and subclinical infections and by continuous exposure to antigens (inhalant allergens, food, etc.). This state of chronic inflammation that characterizes senescence has a significant impact on survival and fragility...
2017: Clinical and Molecular Allergy: CMA
Carolina Obregon, Rajesh Kumar, Manuel Antonio Pascual, Giuseppe Vassalli, Déla Golshayan
Dendritic cells (DCs) as highly efficient antigen-presenting cells are at the interface of innate and adaptive immunity. As such, they are key mediators of immunity and antigen-specific immune tolerance. Due to their functional specialization, research efforts have focused on the characterization of DCs subsets involved in the initiation of immunogenic responses and in the maintenance of tissue homeostasis. Tolerogenic DCs (tolDCs)-based therapies have been designed as promising strategies to prevent and control autoimmune diseases as well as allograft rejection after solid organ transplantation (SOT)...
2017: Frontiers in Immunology
Yangping Wang, Yang Bai, Yashu Li, Guangping Liang, Yufeng Jiang, Zhongyang Liu, Meixi Liu, Jianlei Hao, Xiaorong Zhang, Xiaohong Hu, Jian Chen, Rupeng Wang, Zhinan Yin, Jun Wu, Gaoxing Luo, Weifeng He
Altered homeostasis and dysfunction of dendritic epidermal T cells (DETCs) contribute to abnormal diabetic wound healing. IL-15 plays important roles in survival and activation of T lymphocytes. Recently, reduction of epidermal IL-15 has been reported as an important mechanism for abnormal DETC homeostasis in streptozotocin -induced diabetic animals. However, the role of IL-15 in impaired diabetic wound healing remains unknown. Here, we found that, through rescuing the insufficient activation of DETCs, IL-15 increased IGF-1 production by DETCs and thereby promoted diabetic skin wound repair...
2017: Frontiers in Immunology
Milica Vujicic, Tamara Saksida, Marija Mostarica Stojkovic, Neda Djedovic, Ivana Stojanovic, Stanislava Stosic-Grujicic
Particulate adjuvants have shown increasing promise as effective, safe, and durable agents for the stimulation of immunity, or alternatively, the suppression of autoimmunity. Here we examined the potential of the adjuvant carbonyl iron (CI) for the modulation of organ-specific autoimmune disease-type 1 diabetes (T1D). T1D was induced by multiple low doses of streptozotocin (MLDS) that initiates beta cell death and triggers immune cell infiltration into the pancreatic islets. The results of this study indicate that the single in vivo application of CI to MLDS-treated DA rats, CBA/H mice, or C57BL/6 mice successfully counteracted the development of insulitis and hyperglycemia...
June 2018: Journal of Cellular Physiology
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