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Diabetes and dendritic cells

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https://www.readbyqxmd.com/read/28342735/inhibition-of-effector-antigen-specific-t-cells-by-intradermal-administration-of-heme-oxygenase-1-inducers
#1
Thomas Simon, Julien Pogu, Séverine Rémy, Frédéric Brau, Sylvie Pogu, Maud Maquigneau, Jean-François Fonteneau, Nicolas Poirier, Bernard Vanhove, Gilles Blancho, Eliane Piaggio, Ignacio Anegon, Philippe Blancou
Developing protocols aimed at inhibiting effector T cells would be key for the treatment of T cell-dependent autoimmune diseases including type 1 autoimmune diabetes (T1D) and multiple sclerosis (MS). While heme oxygenase-1 (HO-1) inducers are clinically approved drugs for non-immune-related diseases, they do have immunosuppressive properties when administered systemically in rodents. Here we show that HO-1 inducers inhibit antigen-specific effector T cells when injected intradermally together with the T cell cognate antigens in mice...
March 22, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28291548/the-role-of-interleukin-17a-in-the-pathogenesis-of-kidney-diseases
#2
REVIEW
Charlotte Cortvrindt, Reinhart Speeckaert, Alena Moerman, Joris R Delanghe, Marijn M Speeckaert
Being a member of the IL-17 family, comprising six structurally related ligands, IL-17A is a cytokine, produced by multiple cell types, such as CD4(+)αβ T cells, γδ T cells, natural killer cells, neutrophils, macrophages, dendritic cells, lymphoid tissue inducer cells, mast cells and plasma cells. IL-17A participates in tissue inflammation by inducing the expression of chemokines, proinflammatory cytokines and matrix metalloproteases. Besides its role in host defence against infectious diseases, IL-17A is involved in different autoimmune and inflammatory diseases...
March 10, 2017: Pathology
https://www.readbyqxmd.com/read/28263454/neuroplasticity-of-supraspinal-structures-associated-with-pathological-pain
#3
Pere Boadas-Vaello, Judit Homs, Francisco Reina, Anna Carrera, Enrique Verdú
Peripheral nerve and spinal cord injuries, along with other painful syndromes such as fibromyalgia, diabetic neuropathy, chemotherapeutic neuropathy, trigeminal neuralgia, complex regional pain syndrome, and/or irritable bowel syndrome, cause several neuroplasticity changes in the nervous system along its entire axis affecting the different neuronal nuclei. This paper reviews these changes, focusing on the supraspinal structures that are involved in the modulation and processing of pain, including the periaqueductal gray matter, red nucleus, locus coeruleus, rostral ventromedial medulla, thalamus, hypothalamus, basal ganglia, cerebellum, habenula, primary and secondary somatosensory cortex, motor cortex, mammillary bodies, hippocampus, septum, amygdala, cingulated and prefrontal cortex...
March 6, 2017: Anatomical Record: Advances in Integrative Anatomy and Evolutionary Biology
https://www.readbyqxmd.com/read/28257518/exposure-to-sequestered-self-antigens-in-vivo-is-not-sufficient-for-the-induction-of-autoimmune-diabetes
#4
Nobuyuki Ono, Kiichi Murakami, Olivia Chan, Håkan Hall, Alisha R Elford, Patty Yen, Thomas Calzascia, David M Spencer, Pamela S Ohashi, Salim Dhanji
Although the role of T cells in autoimmunity has been explored for many years, the mechanisms leading to the initial priming of an autoimmune T cell response remain enigmatic. The 'hit and run' model suggests that self-antigens released upon cell death can provide the initial signal for a self-sustaining autoimmune response. Using a novel transgenic mouse model where we could induce the release of self-antigens via caspase-dependent apoptosis. We tracked the fate of CD8+ T cells specific for the self-antigen...
2017: PloS One
https://www.readbyqxmd.com/read/28239381/presentation-of-autoantigen-in-peripheral-lymph-nodes-is-sufficient-for-priming-autoreactive-cd8-t-cells
#5
Nadine Honke, Namir Shaabani, John R Teijaro, Urs Christen, Cornelia Hardt, Judith Bezgovsek, Philipp A Lang, Karl S Lang
Peripheral tolerance is an important mechanism by which the immune system can guarantee a second line of defense against autoreactive T and B cells. One autoimmune disease that is related to a break of peripheral tolerance is diabetes mellitus type 1. Using the RIP-GP mouse model, we analyzed the role of the spleen and lymph nodes (LNs) in priming CD8(+) T cells and breaking peripheral tolerance. We found that diabetes developed in splenectomized mice infected with the lymphocytic choriomeningitis virus (LCMV), a finding showing that the spleen was not necessary in generating autoimmunity...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28237724/the-common-autoimmunity-predisposing-620arg%C3%A2-%C3%A2-trp-variant-of-ptpn22-modulates-macrophage-function-and-morphology
#6
Meihang Li, Hugues Beauchemin, Natalija Popovic, Alan Peterson, Eva d'Hennezel, Ciriaco A Piccirillo, Chao Sun, Constantin Polychronakos
The C1858T single nucleotide polymorphism (SNP) in PTPN22 (protein tyrosine phosphatase nonreceptor 22) leads to the 620 Arg to Trp polymorphism in its encoded human protein LYP. This allelic variant is associated with multiple autoimmune diseases, including type 1 diabetes (T1D), Crohn's disease, rheumatoid arthritis and systemic lupus erythematosus. However, the underlying mechanisms are poorly understood. To study how this polymorphism influences the immune system, we generated a mouse strain with a knock-in of the Trp allele, imitating the human disease-associated variant...
February 22, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28225836/analysis-of-immune-cell-populations-in-atrial-myocardium-of-patients-with-atrial-fibrillation-or-sinus-rhythm
#7
Natalia Smorodinova, Martin Bláha, Vojtěch Melenovský, Karolína Rozsívalová, Jaromír Přidal, Mária Ďurišová, Jan Pirk, Josef Kautzner, Tomáš Kučera
BACKGROUND: Atrial fibrillation (AF) is the most common arrhythmia and despite obvious clinical importance remains its pathogenesis only partially explained. A relation between inflammation and AF has been suggested by findings of increased inflammatory markers in AF patients. OBJECTIVE: The goal of this study was to characterize morphologically and functionally CD45-positive inflammatory cell populations in atrial myocardium of patients with AF as compared to sinus rhythm (SR)...
2017: PloS One
https://www.readbyqxmd.com/read/28213757/germinal-centre-frequency-is-decreased-in-pancreatic-lymph-nodes-from-individuals-with-recent-onset-type-1-diabetes
#8
Abby Willcox, Sarah J Richardson, Lucy S K Walker, Sally C Kent, Noel G Morgan, Kathleen M Gillespie
AIMS/HYPOTHESIS: Pancreatic lymph nodes (PLNs) are critical sites for the initial interaction between islet autoantigens and autoreactive lymphocytes, but the histology of PLNs in tissue from individuals with type 1 diabetes has not been analysed in detail. The aim of this study was to examine PLN tissue sections from healthy donors compared with those at risk of, or with recent-onset and longer-duration type 1 diabetes. METHODS: Immunofluorescence staining was used to examine PLN sections from the following donor groups: non-diabetic (n=15), non-diabetic islet autoantibody-positive (n=5), recent-onset (≤1...
February 17, 2017: Diabetologia
https://www.readbyqxmd.com/read/28201972/cell-based-tolerogenic-therapy-experience-from-animal-models-of-multiple-sclerosis-type-1-diabetes-and-rheumatoid-arthritis
#9
Ivana Stojanović, Mirjana Dimitrijević, Marta Vives-Pi, Maria Jose Mansilla, Irma Pujol-Autonell, Silvia Rodríguez-Fernandez, Lenka Palová-Jelínková, David P Funda, Alisa Gruden-Movsesijan, Ljiljana Sofronić-Milosavljević, Catharien M U Hilkens, Eva Martínez-Cáceres, Djordje Miljković
Cell-based tolerogenic therapy is a promising approach for the treatment of autoimmune diseases and transplant rejection. Regulatory T cells and tolerogenic dendritic cells have been particularly explored in the treatment of various autoimmune disorders in experimental models of disease. Although some of these cells have already been tested in a limited number of clinical trials, there is still a need for preclinical research on tolerogenic cells in animal models of autoimmunity. This review will focus on the relevance of data obtained from studies in experimental animal models for the use of tolerogenic cell-based therapy in humans...
February 14, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28130494/oxidized-low-density-lipoprotein-immune-complex-priming-of-the-nlrp3-inflammasome-involves-tlr-and-fc%C3%AE-r-cooperation-and-is-dependent-on-card9
#10
Jillian P Rhoads, John R Lukens, Ashley J Wilhelm, Jared L Moore, Yanice Mendez-Fernandez, Thirumala-Devi Kanneganti, Amy S Major
Oxidized low-density lipoprotein (oxLDL) is known to activate inflammatory responses in a variety of cells, especially macrophages and dendritic cells. Interestingly, much of the oxLDL in circulation is complexed to Abs, and these resulting immune complexes (ICs) are a prominent feature of chronic inflammatory disease, such as atherosclerosis, type-2 diabetes, systemic lupus erythematosus, and rheumatoid arthritis. Levels of oxLDL ICs often correlate with disease severity, and studies demonstrated that oxLDL ICs elicit potent inflammatory responses in macrophages...
March 1, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28126203/skin-derived-tslp-systemically-expands-regulatory-t-cells
#11
Theresa M Leichner, Atsushi Satake, Victor Sanoe Harrison, Yukinori Tanaka, Angela S Archambault, Brian S Kim, Mark C Siracusa, Warren J Leonard, Ali Naji, Gregory F Wu, David Artis, Taku Kambayashi
Regulatory T cells (Tregs) are a subset of CD4(+) T cells with suppressive function and are critical for limiting inappropriate activation of T cells. Hence, the expansion of Tregs is an attractive strategy for the treatment of autoimmune diseases. Here, we demonstrate that the skin possesses the remarkable capacity to systemically expand Treg numbers by producing thymic stromal lymphopoietin (TSLP) in response to vitamin D receptor stimulation. An ∼2-fold increase in the proportion and absolute number of Tregs was observed in mice treated topically but not systemically with the Vitamin D3 analog MC903...
January 23, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28125531/repeated-binge-like-alcohol-intoxication-depot-specific-adipose-tissue-immuno-metabolic-dysregulation
#12
Flavia M Souza-Smith, Stephen M Ford, Liz Simon, Patricia E Molina
Repeated binge-like alcohol intoxication (RBAI) induces whole-body insulin resistance, which is predicted to increase the risk for metabolic syndrome and type 2 diabetes. Previously we showed that acute alcohol intoxication increases mesenteric lymphatic permeability, perilymphatic adipose tissue (PLAT) inflammation, and circulating lipopolysaccharide (LPS) levels in rats. We hypothesize that mesenteric lymphatic hyperpermeability, adipose tissue inflammation and associated dysregulated adipokine expression and insulin signaling are central mechanisms underlying whole body metabolic dysregulation resulting from RBAI...
January 25, 2017: Shock
https://www.readbyqxmd.com/read/28120714/potential-role-for-dendritic-cells-in-endothelial-dysfunction-diabetes-and-cardiovascular-disease
#13
Astrid Parenti, Laura Pala, Sara Paccosi, Carlo Maria Rotella
BACKGROUND Endothelial dysfunction (ED) is a pathophysiological mechanism present in patients affected by type 2 diabetes (T2DM) supporting the development of cardiovascular disease. Among immune- and inflammatory cells accelerating atherosclerosis, dendritic cells (DC) play a pivotal role, however their pathogenetic mechanism has not been fully clarified, at present. The aim of our review is to explore the relationship between ED, DCs and cardiovascular events. METHODS We analysed the literature in Medline database under ''endothelial function OR dysfunction OR vasodilatation'', AND ''dendritic cells" OR innate immunity" OR "adaptive immunity" AND diabetes AND "cardiovascular disease" OR atherosclerosis"...
January 24, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28116870/multicomponent-injectable-hydrogels-for-antigen-specific-tolerogenic-immune-modulation
#14
Catia S Verbeke, Susana Gordo, David A Schubert, Sarah A Lewin, Rajiv M Desai, Jessica Dobbins, Kai W Wucherpfennig, David J Mooney
Biomaterial scaffolds that enrich and modulate immune cells in situ can form the basis for potent immunotherapies to elicit immunity or reëstablish tolerance. Here, the authors explore the potential of an injectable, porous hydrogel to induce a regulatory T cell (Treg) response by delivering a peptide antigen to dendritic cells in a noninflammatory context. Two methods are described for delivering the BDC peptide from pore-forming alginate gels in the nonobese diabetic mouse model of type 1 diabetes: encapsulation in poly(lactide-co-glycolide) (PLG) microparticles, or direct conjugation to the alginate polymer...
January 24, 2017: Advanced Healthcare Materials
https://www.readbyqxmd.com/read/28106157/tlr4-antagonist-fp7-inhibits-lps-induced-cytokine-production-and-glycolytic-reprogramming-in-dendritic-cells-and-protects-mice-from-lethal-influenza-infection
#15
Laure Perrin-Cocon, Anne Aublin-Gex, Stefania E Sestito, Kari Ann Shirey, Mira C Patel, Patrice André, Jorge C Blanco, Stefanie N Vogel, Francesco Peri, Vincent Lotteau
Dysregulated Toll-like receptor (TLR)-4 activation is involved in acute systemic sepsis, chronic inflammatory diseases, such as atherosclerosis and diabetes, and in viral infections, such as influenza infection. Thus, therapeutic control of the TLR4 signalling pathway is of major interest. Here we tested the activity of the small-molecule synthetic TLR4 antagonist, FP7, in vitro on human monocytes and monocyte-derived dendritic cells (DCs) and in vivo during influenza virus infection of mice. Our results indicate that FP7 antagonized the secretion of proinflammatory cytokines (IL-6, IL-8, and MIP-1β) by monocytes and DCs (IC50 < 1 μM) and prevented DC maturation upon TLR4 activation by ultrapure lipopolysaccharide (LPS)...
January 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28063251/perivascular-adipose-tissue-inflammation-in-vascular-disease
#16
REVIEW
Ryszard Nosalski, Tomasz J Guzik
Perivascular adipose tissue (PVAT) plays a critical role in the pathogenesis of cardiovascular disease. In vascular pathologies perivascular adipose tissue increases in volume and becomes dysfunctional, with altered cellular composition and molecular characteristics. PVAT dysfunction is characterized by its inflammatory character, oxidative stress, diminished production of vaso-protective adipocyte derived relaxing factors (ADRFs) and increased production of paracrine factors such as resistin, leptin, cytokines (IL-6, TNF-α) and chemokines (RANTES, MCP-1)...
January 7, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/27995404/circulating-zonulin-correlates-with-density-of-enteroviruses-and-tolerogenic-dendritic-cells-in-the-small-bowel-mucosa-of-celiac-disease-patients
#17
Tamara Vorobjova, Helerin Raikkerus, Lumme Kadaja, Ija Talja, Oivi Uibo, Kaire Heilman, Raivo Uibo
BACKGROUND: Impaired intestinal integrity, including increased permeability of the small bowel mucosa, has been shown in patients with celiac disease (CD) as well as with type 1 diabetes (T1D). Zonulin (ZO, pre-haptoglobin), a tight junction regulator, plays a particular role in the regulation of intestinal barrier function and in the pathogenesis of the above-mentioned diseases. AIM: To investigate whether enteroviruses (EVs) and immunoregulatory cells are associated with intestinal permeability in patients with CD alone and with coexistent T1D...
December 19, 2016: Digestive Diseases and Sciences
https://www.readbyqxmd.com/read/27990144/glucose-regulated-protein-78-induced-myeloid-antigen-presenting-cells-maintained-tolerogenic-signature-upon-lps-stimulation
#18
Muyang Yang, Fan Zhang, Kai Qin, Min Wu, Heli Li, Huifen Zhu, Qin Ning, Ping Lei, Guanxin Shen
The 78-kDa glucose-regulated protein (Grp78) is stress-inducible chaperone that mostly reside in the endoplasmic reticulum. Grp78 has been described to be released at times of cellular stress and as having extracellular properties that are anti-inflammatory or favor the resolution of inflammation. As antigen-presenting cells (APCs) play a critical role in both the priming of adaptive immune responses and the induction of self-tolerance, herein, we investigated the effect of Grp78 on the maturation of murine myeloid APCs (CD11c(+) cells)...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27927966/tolerogenic-dendritic-cells-from-poorly-compensated-type-1-diabetes-patients-have-decreased-ability-to-induce-stable-antigen-specific-t-cell-hyporesponsiveness-and-generation-of-suppressive-regulatory-t-cells
#19
Klára Dáňová, Anna Grohová, Pavla Strnadová, David P Funda, Zdeněk Šumník, Jan Lebl, Ondřej Cinek, Štěpánka Průhová, Stanislava Koloušková, Barbora Obermannová, Lenka Petruželková, Anna Šedivá, Petra Fundová, Karsten Buschard, Radek Špíšek, Lenka Palová-Jelínková
Tolerogenic dendritic cells (tolDCs) may offer an interesting intervention strategy to re-establish Ag-specific tolerance in autoimmune diseases, including type 1 diabetes (T1D). T1D results from selective destruction of insulin-producing β cells leading to hyperglycemia that, in turn, specifically affects a patient's immune system. In this study, we prepared monocyte-derived tolDCs modulated by dexamethasone and vitamin D2 from 31 T1D patients with optimal glycemic control and 60 T1D patients with suboptimal glycemic control and assessed their tolerogenic properties in correlation with metabolic state of patients...
December 7, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27926736/structure-of-cc-chemokine-receptor-2-with-orthosteric-and-allosteric-antagonists
#20
Yi Zheng, Ling Qin, Natalia V Ortiz Zacarías, Henk de Vries, Gye Won Han, Martin Gustavsson, Marta Dabros, Chunxia Zhao, Robert J Cherney, Percy Carter, Dean Stamos, Ruben Abagyan, Vadim Cherezov, Raymond C Stevens, Adriaan P IJzerman, Laura H Heitman, Andrew Tebben, Irina Kufareva, Tracy M Handel
CC chemokine receptor 2 (CCR2) is one of 19 members of the chemokine receptor subfamily of human class A G-protein-coupled receptors. CCR2 is expressed on monocytes, immature dendritic cells, and T-cell subpopulations, and mediates their migration towards endogenous CC chemokine ligands such as CCL2 (ref. 1). CCR2 and its ligands are implicated in numerous inflammatory and neurodegenerative diseases including atherosclerosis, multiple sclerosis, asthma, neuropathic pain, and diabetic nephropathy, as well as cancer...
December 15, 2016: Nature
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