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https://www.readbyqxmd.com/read/29784651/immune-recognition-of-%C3%AE-cells-neoepitopes-as-key-players-in-the-loss-of-tolerance
#1
Eddie A James, Massimo Pietropaolo, Mark J Mamula
Prior to the onset of type 1 diabetes, there is progressive loss of immune self-tolerance, evidenced by the accumulation of islet autoantibodies and emergence of autoreactive T cells. Continued autoimmune activity leads to the destruction of pancreatic β-cells and loss of insulin secretion. Studies of samples from patients with type 1 diabetes and of murine disease models have generated important insights about genetic and environmental factors that contribute to susceptibility and immune pathways that are important for pathogenesis...
June 2018: Diabetes
https://www.readbyqxmd.com/read/29778842/curcumin-attenuates-sepsis-induced-acute-organ-dysfunction-by-preventing-inflammation-and-enhancing-the-suppressive-function-of-tregs
#2
Longwang Chen, Yang Lu, Linjun Zhao, Lili Hu, Qiaomeng Qiu, Zhuoling Zhang, Mengfang Li, Guangliang Hong, Bing Wu, Guangju Zhao, Zhongqiu Lu
Sepsis is characterized by the extensive release of cytokines and other mediators. It results in a dysregulated immune response and can lead to organ damage and death. Curcumin has anti-inflammatory properties and immunoregulation functions in various disorders such as sepsis, cancer, rheumatoid arthritis, cardiovascular diseases, lung fibrosis, gallstone formation, and diabetes. This paper investigates the effects of curcumin on immune status and inflammatory response in mice subjected to cecal ligation and puncture (CLP)...
May 17, 2018: International Immunopharmacology
https://www.readbyqxmd.com/read/29774468/salivary-anti-coxsackievirus-b4-neutralizing-activity-and-pattern-of-immune-parameters-in-patients-with-type-1-diabetes-a-pilot-study
#3
Magloire Pandoua Nekoua, Akadiri Yessoufou, Enagnon Kazali Alidjinou, Francis Badia-Boungou, Kabirou Moutairou, Famara Sane, Didier Hober
AIMS: Enteroviruses, especially coxsackieviruses B (CV-B), have been associated with the pathogenesis of type 1 diabetes (T1D). An anti-CV-B4 neutralizing activity in saliva of T1D patients was previously reported. Our aim was to study the association between the saliva anti-CV-B4 neutralizing activity and immune parameters in T1D patients in comparison with non-diabetic individuals. METHODS: Saliva and blood samples were collected from 15 T1D patients and 8 controls...
May 17, 2018: Acta Diabetologica
https://www.readbyqxmd.com/read/29774025/co-stimulation-impaired-bone-marrow-derived-dendritic-cells-prevent-dextran-sodium-sulfate-induced-colitis-in-mice
#4
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
#5
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/29757588/association-of-regulatory-t-cells-with-diabetes-type-1-and-its-renal-and-vascular-complications-based-on-the-expression-of-forkhead-box-protein-p3-foxp3-helios-and-neurophilin-1
#6
Tahereh Khamechian, Behnaz Irandoust, Hanieh Mohammadi, Hassan Nikoueinejad, Hossein Akbari
In recent years, it has been recognized that regulatory T cells (Tregs) play a critical role in maintaining immune tolerance. Moreover, the expression of two markers named Helios and neurophilin-1 (NRP-1) has been highlighted in such cells. Helios, an intracellular transcription marker, largely differentiates twomost operative sub group of Tregs, namely naturally occurring (nTreg) and induced (iTreg) Tregs, and NRP-1 is reckoned as a membranous activity marker of Tregs. We aimed to count peripheral mononuclear cells expressing such markers in a group of type 1 diabetes patients to elucidate the possible role of Tregs in the pathogenesis of such disease and its complications...
April 2018: Iranian Journal of Allergy, Asthma, and Immunology
https://www.readbyqxmd.com/read/29750331/salivary-gland-protective-regulatory-t-cell-dysfunction-underlies-female-specific-sialadenitis-in-the-nonobese-diabetic-mouse-model-of-sj%C3%A3-gren-syndrome
#7
Jennifer Y Barr, Xiaofang Wang, Portia A Kreiger, Scott M Lieberman
Immune cell-mediated destruction of salivary glands is a hallmark feature of Sjögren syndrome. Similar to the female predominance in humans, female nonobese diabetic (NOD) mice develop spontaneous salivary gland autoimmunity. However, in both humans and mice it is unclear what factors contribute to the initial immune infiltration of the salivary glands. Here, we used an adoptive transfer model of Sjögren syndrome to determine if female mice harbor a sex-specific defect in salivary gland-protective regulatory T (Treg) cells...
May 11, 2018: Immunology
https://www.readbyqxmd.com/read/29743501/a-phase-i-clinical-trial-with-ex-vivo-expanded-recipient-regulatory-t-cells-in-living-donor-kidney-transplants
#8
James M Mathew, Jessica H-Voss, Ann LeFever, Iwona Konieczna, Cheryl Stratton, Jie He, Xuemei Huang, Lorenzo Gallon, Anton Skaro, Mohammed Javeed Ansari, Joseph R Leventhal
There is considerable interest in therapeutic transfer of regulatory T cells (Tregs) for controlling aberrant immune responses. Initial clinical trials have shown the safety of Tregs in hematopoietic stem cell transplant recipients and subjects with juvenile diabetes. Our hypothesis is that infusion(s) of Tregs may induce transplant tolerance thus avoiding long-term use of toxic immunosuppressive agents that cause increased morbidity/mortality. Towards testing our hypothesis, we conducted a phase I dose escalation safety trial infusing billions of ex vivo expanded recipient polyclonal Tregs into living donor kidney transplant recipients...
May 9, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29732719/evaluation-of-visceral-adipose-tissue-oxygenation-by-blood-oxygen-level-dependent-mri-in-zucker-diabetic-fatty-rats
#9
Hong-Jian Shi, Yan-Feng Li, Wen-Jie Ji, Zhi-Chun Lin, Wei Cai, Tao Chen, Bin Yuan, Xiu-Long Niu, Han-Ying Li, Wen Shu, Yu-Ming Li, Fei Yuan, Xin Zhou, Zhuoli Zhang
OBJECTIVE: This study aimed to investigate the feasibility of blood oxygen level-dependent magnetic resonance imaging (BOLD-MRI) to evaluate visceral adipose tissue (VAT) oxygenation in Zucker diabetic fatty (ZDF) rats and its associations with systemic metaflammation. METHODS: Five-week-old ZDF rats and Zucker lean (ZL) rats were fed a high-fat diet (HFD) for 18 weeks. A baseline BOLD-MRI scan of perirenal adipose tissue was performed after 8 weeks of HFD feeding, and then the rats were randomized to receive pioglitazone or a vehicle for the following 10 weeks...
May 7, 2018: Obesity
https://www.readbyqxmd.com/read/29722336/mitochondrial-autophagy-and-nlrp3-inflammasome-in-pulmonary-tissues-from-severe-combined-immunodeficient-mice-after-cardiac-arrest-and-cardiopulmonary-resuscitation
#10
Jing-Jun Lyu, Jawahar L Mehta, Yi Li, Lu Ye, Sheng-Nan Sun, Hong-Shuang Sun, Jia-Chang Li, Dong-Mei Zhang, Jie Wei
Background: The incidence of cancer, diabetes, and autoimmune diseases has been increasing. Furthermore, there are more and more patients with solid organ transplants. The survival rate of these immunocompromised individuals is extremely low when they are severely hit-on. In this study, we established cardiac arrest cardiopulmonary resuscitation (CPR) model in severe combined immunodeficient (SCID) mice, analyzed the expression and activation of mitochondrial autophagy and NLRP3 inflammasome/caspase-1, and explored mitochondrial repair and inflammatory injury in immunodeficiency individual during systemic ischemia-reperfusion injury...
May 20, 2018: Chinese Medical Journal
https://www.readbyqxmd.com/read/29712852/revealing-the-specificity-of-regulatory-t-cells-in-murine-autoimmune-diabetes
#11
Allyson Spence, Whitney Purtha, Janice Tam, Shen Dong, Youmin Kim, Chia-Hsin Ju, Teague Sterling, Maki Nakayama, William H Robinson, Jeffrey A Bluestone, Mark S Anderson, Qizhi Tang
Regulatory T cells (Tregs) control organ-specific autoimmunity in a tissue antigen-specific manner, yet little is known about their specificity in a natural repertoire. In this study, we used the nonobese diabetic (NOD) mouse model of autoimmune diabetes to investigate the antigen specificity of Tregs present in the inflamed tissue, the islets of Langerhans. Compared with Tregs present in spleen and lymph node, Tregs in the islets showed evidence of antigen stimulation that correlated with higher proliferation and expression of activation markers CD103, ICOS, and TIGIT...
April 30, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29697291/vildagliptin-recruits-regulatory-t-cells-in-patients-undergoing-primary-percutaneous-coronary-intervention
#12
Fatma H Rizk, Muhammad Tarek Abdel Ghafar, Nema A Soliman, Aliaa E Shaaban, Ramy Atlam, Amiraa Elsaadany, Kareman Ahmed Eshra, Marwa Mostafa Shalaby
Regulatory T cells (Treg) has been documented to be protective against myocardial ischemia-reperfusion injury (MIRI). The administration of drugs which recruit Treg cells may participate in the cardioprotection of MIRI. The purpose of the present study was to investigate whether the add-on vildagliptin (vild) to standard treatment of MIRI prior to reperfusion could increase Treg recruitment, anti-inflammatory, and antioxidant effects of the standard treatment or not. Sixty diabetic patients with ST-segment elevation myocardial infarction were randomly divided into two equal groups: control group was given the standard medical treatment and vild group was given the standard medical treatment plus vild...
April 26, 2018: Immunological Investigations
https://www.readbyqxmd.com/read/29696366/genetic-interaction-between-two-insulin-dependent-diabetes-susceptibility-loci-idd2-and-idd13-in-determining-immunoregulatory-dn-t-cell-proportion
#13
Roxanne Collin, Kathy Doyon, Victor Mullins-Dansereau, Martin Karam, Geneviève Chabot-Roy, Erin E Hillhouse, Alexandre Orthwein, Sylvie Lesage
Several immune regulatory cell types participate in the protection against autoimmune diseases such as autoimmune diabetes. Of these immunoregulatory cells, we and others have shown that peripheral CD4- CD8- double negative (DN) T cells can induce antigen-specific immune tolerance. Particularly, we have described that diabetes-prone mice exhibit a lower number of peripheral DN T cells compared to diabetes-resistant mice. Identifying the molecular pathways that influence the size of the DN T cell pool in peripheral lymphoid organs may thus be of interest for maintaining antigen-specific immune tolerance...
April 25, 2018: Immunogenetics
https://www.readbyqxmd.com/read/29691600/a-proinflammatory-cd4-t-cell-phenotype-in-gestational-diabetes-mellitus
#14
Angela Sheu, Yixian Chan, Angela Ferguson, Mohammad B Bakhtyari, Wendy Hawke, Chris White, Yuk Fun Chan, Patrick J Bertolino, Heng G Woon, Umaimainthan Palendira, Frederic Sierro, Sue Mei Lau
AIMS/HYPOTHESIS: Numerous adaptations of the maternal immune system are necessary during pregnancy to maintain immunological tolerance to the semi-allogeneic fetus. Several complications of pregnancy have been associated with dysregulation of these adaptive mechanisms. While gestational diabetes mellitus (GDM) has been associated with upregulation of circulating inflammatory factors linked to innate immunity, polarisation of the adaptive immune system has not been extensively characterised in this condition...
April 24, 2018: Diabetologia
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
#15
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/29625181/hyaluronan-in-immune-dysregulation-and-autoimmune-diseases
#16
REVIEW
Nadine Nagy, Hedwich F Kuipers, Payton L Marshall, Esther Wang, Gernot Kaber, Paul L Bollyky
The tissue microenvironment contributes to local immunity and to the pathogenesis of autoimmune diseases - a diverse set of conditions characterized by sterile inflammation, immunity against self-antigens, and destruction of tissues. However, the specific factors within the tissue microenvironment that contribute to local immune dysregulation in autoimmunity are poorly understood. One particular tissue component implicated in multiple autoimmune diseases is hyaluronan (HA), an extracellular matrix (ECM) polymer...
April 3, 2018: Matrix Biology: Journal of the International Society for Matrix Biology
https://www.readbyqxmd.com/read/29615971/impact-of-glucose-loading-on-variations-in-cd4-and-cd8-t-cells-in-japanese-participants-with-or-without-type-2-diabetes
#17
Aika Miya, Akinobu Nakamura, Hideaki Miyoshi, Yoshinari Takano, Kana Sunagoya, Koji Hayasaka, Chikara Shimizu, Yasuo Terauchi, Tatsuya Atsumi
Objective: The aim of this study was to examine the fluctuations in CD4+ T cells, CD8+ T cells, and natural CD4+ CD25+ FoxP3+ T-regulatory (Treg) cells following an oral glucose tolerance test (OGTT) in participants with and those without type 2 diabetes (T2DM). Methods: 19 Japanese participants with T2DM (DM group) and 21 participants without diabetes (non-DM group) were recruited and underwent a 75-g OGTT. The cell numbers of leukocytes, lymphocytes, and the T cell compartment, such as CD4+ , CD8+ , and Treg, were calculated for blood samples obtained after an overnight 12 h fast and during a 75-g OGTT at 60 and 120 min...
2018: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/29604048/peripherally-induced-regulatory-t-cells-contribute-to-the-control-of-autoimmune-diabetes-in-the-nod-mouse-model
#18
Cornelia Schuster, Franziska Jonas, Fangzhu Zhao, Stephan Kissler
Type 1 diabetes (T1D) results from the autoimmune destruction of pancreatic beta cells and is partly caused by deficiencies in the Foxp3+ regulatory T-cell (Treg) compartment. Conversely, therapies that increase Treg function can prevent autoimmune diabetes in animal models. The majority of Tregs develop in the thymus (tTregs), but a proportion of Foxp3+ Tregs is generated in the periphery (pTregs) from Foxp3- CD4+ T-cell precursors. Whether pTregs play a distinct role in T1D has not yet been explored. We report here that pTregs are a key modifier of disease in the nonobese diabetic (NOD) mouse model for T1D...
March 31, 2018: European Journal of Immunology
https://www.readbyqxmd.com/read/29603313/cd38-protein-deficiency-induces-autoimmune-characteristics-and-its-activation-enhances-il-10-production-by-regulatory-b-cells
#19
Marilú Domínguez-Pantoja, Gabriela López-Herrera, Héctor Romero-Ramírez, Leopoldo Santos-Argumedo, Adriana K Chávez-Rueda, Ángeles Hernández-Cueto, Mónica Flores-Muñoz, Juan C Rodríguez-Alba
CD38 is a transmembrane protein expressed in B lymphocytes, that is able to induce responses as proliferation, differentiation or apoptosis. Several reports propose that CD38 deficiency accelerates autoimmune processes in murine models of autoimmune diabetes, lymphoproliferation, and rheumatoid arthritis. Other reports have shown elevated CD38 expression in B and T cells from patients with autoimmunity; however, the role of CD38 is still unclear in the development of autoimmunity. Recently, it has been characterized as CD1dhi CD5+ regulatory B cell subpopulation able to produce IL-10, and the loss of this cells exacerbate the autoimmunity in murine models...
March 30, 2018: Scandinavian Journal of Immunology
https://www.readbyqxmd.com/read/29594371/b-cell-depletion-reduces-t-cell-activation-in-pancreatic-islets-in-a-murine-autoimmune-diabetes-model
#20
Larissa C Da Rosa, Joanne Boldison, Evy De Leenheer, Joanne Davies, Li Wen, F Susan Wong
AIMS/HYPOTHESIS: Type 1 diabetes is a T cell-mediated autoimmune disease characterised by the destruction of beta cells in the islets of Langerhans, resulting in deficient insulin production. B cell depletion therapy has proved successful in preventing diabetes and restoring euglycaemia in animal models of diabetes, as well as in preserving beta cell function in clinical trials in the short term. We aimed to report a full characterisation of B cell kinetics post B cell depletion, with a focus on pancreatic islets...
March 28, 2018: Diabetologia
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