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Diabetes and dendritic cells

Huiting Su, Ning Na, Xiaodong Zhang, Yong Zhao
CD74 (MHC class II invariant chain, Ii) is a non-polymorphic type II transmembrane glycoprotein. It is clear that, in addition to be an MHC class II chaperone, CD74 has a diversity of biological functions in physiological and pathological situations. CD74 also participates in other non-MHC II protein trafficking, such as angiotensin II type I receptor. In addition, CD74 is a cell membrane high-affinity receptor for macrophage migration inhibitory factor (MIF), D-dopachrome tautomerase (D-DT/MIF-2) and bacterial proteins...
October 17, 2016: Inflammation Research: Official Journal of the European Histamine Research Society ... [et Al.]
Kevin V Chow, Emma M Carrington, Yifan Zhan, Andrew M Lew, Robyn M Sutherland
Islet transplantation can cure type 1 diabetes, but is limited by lack of donor organs and early graft dysfunction, such that many patients require multiple transplants to achieve insulin independence. Monocyte derived dendritic cells (moDCs) arise during inflammation and allograft encounters where they can promote various innate and adaptive immune responses. To determine whether moDCs impair early graft function following allogeneic islet transplantation, we transplanted MHC-mismatched BALB/c (H-2d) islets into diabetic C57BL/6-CCR2...
October 13, 2016: Cell Transplantation
John F Trant, Namrata Jain, Delfina M Mazzuca, James T McIntosh, Bo Fan, S M Mansour Haeryfar, Sebastien Lecommandoux, Elizabeth R Gillies
Nanoassemblies presenting multivalent displays of biologically active carbohydrates are of significant interest for a wide array of biomedical applications ranging from drug delivery to immunotherapy. In this study, glycodendron-lipid hybrids were developed as a new and tunable class of dendritic amphiphiles. A modular synthesis was used to prepare dendron-lipid hybrids comprising distearylglycerol and 0 through 4th generation polyester dendrons with peripheral protected amines. Following deprotection of the amines, an isothiocyanate derivative of C-linked α-galactose (α-Gal) was conjugated to the dendron peripheries, affording amphiphiles with 1 to 16 α-Gal moieties...
October 14, 2016: Nanoscale
Javier A Carrero, Stephen T Ferris, Emil R Unanue
Islets of Langerhans of all species harbor a small number of resident macrophages. These macrophages are found since birth, do not exchange with blood monocytes, and are maintained by a low level of replication. Under steady state conditions, the islet macrophages are in an activated state. Islet macrophages have an important homeostatic role in islet physiology. At the start of the autoimmune process in the NOD mouse, a small number of CD103+ dendritic cells (DC) are found at about the same time that CD4+ T cells also appear in islets...
October 3, 2016: Current Opinion in Immunology
Yuriko Itzel Sánchez-Zamora, Imelda Juarez-Avelar, Alicia Vazquez-Mendoza, Marcia Hiriart, Miriam Rodriguez-Sosa
Macrophage migration inhibitory factor (Mif) is highly expressed in type 1 diabetes mellitus (T1DM). However, there is limited information about how Mif influences the activation of macrophages (Mφ) and dendritic cells (DC) in T1DM. To address this issue, we induced T1DM by administering multiple low doses of streptozotocin (STZ) to Mif-/- or wild-type (Wt) BALB/c mice. We found that Mif-/- mice treated with STZ (Mif-/-STZ) developed lower levels of hyperglycemia, inflammatory cytokines, and specific pancreatic islet antigen- (PIAg-) IgG and displayed reduced cellular infiltration into the pancreatic islets compared to Wt mice treated with STZ (WtSTZ)...
2016: Journal of Diabetes Research
Weirong Chen, Xiaoxiao Wan, Tobechukwu K Ukah, Mindy M Miller, Subhasis Barik, Alexis N Cattin-Roy, Habib Zaghouani
To contain autoimmunity, pathogenic T cells must be eliminated or diverted from reaching the target organ. Recently, we defined a novel form of T cell tolerance whereby treatment with Ag downregulates expression of the chemokine receptor CXCR3 and prevents diabetogenic Th1 cells from reaching the pancreas, leading to suppression of type 1 diabetes (T1D). This report defines the signaling events underlying Ag-induced chemokine receptor-mediated tolerance. Specifically, we show that the mammalian target of rapamycin complex 1 (mTORC1) is a major target for induction of CXCR3 downregulation and crippling of Th1 cells...
September 26, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
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...
September 12, 2016: Journal of Autoimmunity
Elzbieta Skowronska-Jozwiak, Stanislaw Sporny, Joanna Szymanska-Duda, Dominika Baranowska, Andrzej Lewinski
Langerhans cell histiocytosis (LCH) in adults is a rare disorder of unknown etiology characterized by monoclonal proliferation of Langerhans cells. It belongs to dendritic cell disorders and occurs in 1-2 adults per million. The most common endocrine manifestation of classical LCH is associated with the posterior pituitary, with clinical symptoms of diabetes insipidus. Less than 80 reported cases of LCH involving the thyroid gland have been published so far. We present the case of a 39 years old woman with 10 years history of diabetes insipidus and secondary amenorrhoea, which appeared after second delivery...
July 12, 2016: Neuro Endocrinology Letters
Naiara N Dejani, Stephanie L Brandt, Annie Piñeros, Nicole L Glosson-Byers, Sue Wang, Young Min Son, Alexandra I Medeiros, C Henrique Serezani
Diabetics are more prone to Staphylococcus aureus skin infection than healthy individuals. Control of S. aureus infection is dependent on dendritic cell (DC)-induced Th17-mediated neutrophil recruitment and bacterial clearance. DC ingestion of infected apoptotic cells (IAC) drive prostaglandin E2 (PGE2) secretion to generate Th17 cells. We speculated that hyperglycemia inhibits skin DC migration to the lymph nodes (LNs) and impairs Th17 differentiation that accounts for poor skin host defense in diabetic mice...
September 7, 2016: Diabetes
Lisa H Tostanoski, Yu-Chieh Chiu, James I Andorko, Ming Guo, Xiangbin Zeng, Peipei Zhang, Walter Royal Iii, Christopher M Jewell
Recent studies demonstrate that excess signaling through inflammatory pathways (e.g., toll-like receptors, TLRs) contributes to the pathogenesis of human autoimmune diseases, including lupus, diabetes, and multiple sclerosis (MS). We hypothesized that co-delivery of a regulatory ligand of TLR9, GpG oligonucleotide, along with myelin - the "self" molecule attacked in MS - might restrain the pro-inflammatory signaling typically present during myelin presentation, redirecting T cell differentiation away from inflammatory populations and towards tolerogenic phenotypes such as regulatory T cells...
August 31, 2016: ACS Nano
Piangkwan Sa-Nguanmoo, Pongpan Tanajak, Sasiwan Kerdphoo, Pattarapong Satjaritanun, Xiaojie Wang, Guang Liang, Xiaokun Li, Chao Jiang, Wasana Pratchayasakul, Nipon Chattipakorn, Siriporn C Chattipakorn
Fibroblast growth factor 21 (FGF21) is an endocrine hormone which exerts beneficial effects on metabolic regulation in obese and diabetic models. However, the effect of FGF21 on cognition in obese-insulin resistant rats has not been investigated. We hypothesized that FGF21 prevented cognitive decline in obese-insulin resistant rats by improving hippocampal synaptic plasticity, dendritic spine density, brain mitochondrial function and brain FGF21 signaling as well as decreasing brain cell apoptosis. Eighteen male Wistar rats were divided into two groups, and received either a normal diet (ND) (n=6) or a high fat diet (HFD) (n=12) for 12weeks...
September 2016: Hormones and Behavior
Cheryl Stroud, Igor Dmitriev, Elena Kashentseva, Jeffrey N Bryan, David T Curiel, Hans Rindt, Carol Reinero, Carolyn J Henry, Philip J Bergman, Nicola J Mason, Josephine S Gnanandarajah, Julie B Engiles, Falon Gray, Danielle Laughlin, Anita Gaurnier-Hausser, Anu Wallecha, Margie Huebner, Yvonne Paterson, Daniel O'Connor, Laura S Treml, James P Stannard, James L Cook, Marc Jacobs, Gerald J Wyckoff, Lee Likins, Ubadah Sabbagh, Andrew Skaff, Amado S Guloy, Harlen D Hays, Amy K LeBlanc, Joan R Coates, Martin L Katz, Leslie A Lyons, Gayle C Johnson, Gary S Johnson, Dennis P O'Brien, Dongsheng Duan, James P Calvet, Barbara Gandolfi, David A Baron, Mark L Weiss, Debra A Webster, Francis N Karanu, Edward J Robb, Robert J Harman
A1 One health advances and successes in comparative medicine and translational researchCheryl StroudA2 Dendritic cell-targeted gorilla adenoviral vector for cancer vaccination for canine melanomaIgor Dmitriev, Elena Kashentseva, Jeffrey N. Bryan, David T. CurielA3 Viroimmunotherapy for malignant melanoma in the companion dog modelJeffrey N. Bryan, David Curiel, Igor Dmitriev, Elena Kashentseva, Hans Rindt, Carol Reinero, Carolyn J. HenryA4 Of mice and men (and dogs!): development of a commercially licensed xenogeneic DNA vaccine for companion animals with malignant melanomaPhilip J...
August 2016: Clinical and Translational Medicine
Sandeep Sundara Rajan, Maria Paula Longhi
Visceral adipose tissue inflammation in obesity is an established risk factor for metabolic syndrome, which can include insulin resistance, type 2 diabetes, hypertension and cardiovascular diseases. With obesity and related metabolic disorders reaching epidemic proportions globally, an understanding of the mechanisms of adipose tissue inflammation is crucial. Within the immune cell cohort, dendritic cells (DCs) play a key role in balancing tolerance and immunity. Despite decades of research into the characterization of DCs in lymphoid and non-lymphoid organs, their role in adipose tissue function is poorly understood...
August 1, 2016: Immunology
Sara Pratesi, Francesca Nencini, Lucia Filì, Ernesto G Occhiato, Sergio Romagnani, Paola Parronchi, Enrico Maggi, Alessandra Vultaggio
8-OH modified adenine bound to Dermatophagoides pteronyssinus group 2 (nDer p2-Conj), a novel allergen-TLR7 agonist conjugate, improves murine airway inflammation in priming and therapeutic settings, however no data are known on the activity of this construct on Th17 cells. The aim of the study was to evaluate if nDer p2-Conj elicited in vivo Th17 cells and Th17-driven autoimmune responses, by using both short- and long-term priming and therapeutic protocols in a nDer p2-driven model of murine airway inflammation...
September 2016: Molecular Immunology
Lindsey E Padgett, Hubert M Tse
Originally recognized for their direct induced toxicity as a component of the innate immune response, reactive oxygen species (ROS) can profoundly modulate T cell adaptive immune responses. Efficient T cell activation requires: signal 1, consisting of an antigenic peptide-MHC complex binding with the TCR; signal 2, the interaction of costimulatory molecules on T cells and APCs; and signal 3, the generation of innate immune-derived ROS and proinflammatory cytokines. This third signal, in particular, has proven essential in generating productive and long-lasting immune responses...
September 1, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
Takeshi Itoh, Yuko Hata, Hitomi Nishinakamura, Kenjiro Kumano, Hiroyuki Takahashi, Shohta Kodama
BACKGROUND: Clinical allogeneic islet transplantation has become an attractive procedure for type 1 diabetes mellitus treatment. However, there is a severe shortage of human donors. Microencapsulated neonatal porcine islet (NPI) xenotransplantation may be an alternative transplantation procedure. Currently, the efficacy of microencapsulated NPI xenotransplantation into the peritoneal cavity is limited because of early non-function resulting from inflammation, which is a serious hindrance to promoting this procedure as a standard therapy...
September 2016: Xenotransplantation
K Paul, S Franke, J Nadal, M Schmid, A Yilmaz, D Kretzschmar, B Bärthlein, S Titze, A Koettgen, G Wolf, M Busch
Decreased blood dendritic cell precursors (DCP) count is linked with atherosclerotic disease, while reduction of circulating DCP is also seen in patients with chronic kidney disease (CKD). As poor vitamin D status could be linked to a compromised innate immune response, we hypothesized that vitamin D status might be involved in the decrease in circulating DCP in CKD. Moreover, the potential role of inflammation was considered. Circulating myeloid (mDCP), plasmacytoid (pDCP) and total DCP (tDCP) were analysed using flow cytometry in 287 patients with CKD stage 3...
October 2016: Clinical and Experimental Immunology
Muhammed Yuksel, Xiaoyan Xiao, Ningwen Tai, Godhev Manakkat Vijay, Elke Gülden, Kathie Beland, Pascal Lapierre, Fernando Alvarez, Zhao Hu, Isabelle Colle, Yun Ma, Li Wen
Autoimmune hepatitis (AIH) is a chronic liver disease characterized by progressive inflammation, female preponderance and seropositivity for autoantibodies such as anti-smooth muscle actin and/or anti-nuclear, anti-liver kidney microsomal type 1 (anti-LKM1) and anti-liver cytosol type 1 (anti-LC1) in over 80% of cases. AIH is strongly linked to several MHC alleles including HLA-DR3, -DR7 and -DR13. HLA-DR4 has the second strongest association with adult AIH, after HLA-DR3. We investigated the role of HLA-DR4 in the development of AIH by immunization of HLA-DR4 (DR4) transgenic non-obese diabetic (NOD) mice with DNA coding for human CYP2D6/FTCD fusion autoantigen...
July 14, 2016: Clinical and Experimental Immunology
Jessica A Pane, Fiona E Fleming, Kate L Graham, Helen E Thomas, Thomas W H Kay, Barbara S Coulson
Rotavirus infection is associated with childhood progression to type 1 diabetes. Infection by monkey rotavirus RRV accelerates diabetes onset in non-obese diabetic (NOD) mice, which relates to regional lymph node infection and a T helper 1-specific immune response. When stimulated ex vivo with RRV, plasmacytoid dendritic cells (pDCs) from naïve NOD mice secrete type I interferon, which induces the activation of bystander lymphocytes, including islet-autoreactive T cells. This is our proposed mechanism for diabetes acceleration by rotaviruses...
2016: Scientific Reports
Lisa H Tostanoski, Emily A Gosselin, Christopher M Jewell
Autoimmune diseases occur when cells of the adaptive immune system incorrectly recognize and attack "self" tissues. Importantly, the proliferation and differentiation of these cells is triggered and controlled by interactions with antigen presenting cells (APCs), such as dendritic cells. Thus, modulating the signals transduced by APCs (e.g., cytokines, costimulatory surface proteins) has emerged as a promising strategy to promote tolerance for diseases such as multiple sclerosis, type 1 diabetes, and lupus...
May 2016: Discovery Medicine
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