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https://www.readbyqxmd.com/read/29155454/harnessing-the-power-of-regulatory-t-cells-to-control-autoimmune-diabetes-overview-and-perspective
#1
REVIEW
Hua Yu, Ricardo Paiva, Richard A Flavell
Type 1 diabetes (T1D) is a T cell-mediated autoimmune disease resulting in islet β-cell destruction, hypoinsulinemia, and severely altered glucose homeostasis. Although the mechanisms that initiate T1D still remain elusive, a breakdown of immune tolerance between effector T cells (Teff) and regulatory T cells (Treg) is considered to be the crucial component leading to autoimmunity. As such, strategies have been developed to boost the number and/or function of Treg in the hope of specifically hampering the pathogenic Teff activity...
November 20, 2017: Immunology
https://www.readbyqxmd.com/read/29149782/frequency-of-circulatory-regulatory-immune-cells-in-iranian-patients-with-type-1-diabetes
#2
Tahereh Khamehchian, Eqlim Nemati, Marziyeh Jazayeri, Shirin Azimi, Hassan Nikoueinejad, Hossein Akbari, Behnaz Irandoust
Type 1 diabetes (T1D) is the result of the autoimmune destruction of insulin-producing beta cells. Regulatory T cells (Tregs) and plasmacytoid dendritic cells (PDCs) act as mediators of peripheral tolerance. We investigated the possible alterations of such cells in peripheral blood of patients with T1D compared to normal individuals. This comparison may lead to a better understanding of the immunopathogenesis processes involved in T1D. 92 participants, including 49 patients with T1D and 43 healthy controls were studied...
October 2017: Iranian Journal of Allergy, Asthma, and Immunology
https://www.readbyqxmd.com/read/29141759/cell-type-specific-immunomodulation-induced-by-helminthes-effect-on-metainflammation-insulin-resistance-and-type-2-diabetes
#3
Vivekanandhan Aravindhan, Gowrishankar Anand
Recent epidemiological studies have documented an inverse relationship between the decreasing prevalence of helminth infections and the increasing prevalence of metabolic diseases ("metabolic hygiene hypothesis"). Chronic inflammation leading to insulin resistance (IR) has now been identified as a major etiological factor for a variety of metabolic diseases other than obesity and Type-2 diabetes (metainflammation). One way by which helminth infections such as filariasis can modulate IR is by inducing a chronic, nonspecific, low-grade, immune suppression mediated by modified T-helper 2 (Th2) response (induction of both Th2 and regulatory T cells) which can in turn suppress the proinflammatory responses and promote insulin sensitivity (IS)...
October 30, 2017: American Journal of Tropical Medicine and Hygiene
https://www.readbyqxmd.com/read/29136611/gut-microbiota-in-health-and-disease
#4
Yuichiro Yamashiro
Intestinal regulatory T (Treg) cells are critical to maintaining immune tolerance to dietary antigens and gut microbiota. This paper reviews several papers on this topic that were recently published by Japanese researchers. Specifically, Prof. K. Honda and his group have found that commensal microbiota capable of metabolizing butyrate induces the differentiation of colonic Treg cells. In a separate work, Prof. Y. Yokoyama and his group used a novel, culture-independent analytical method (the Yakult Intestinal Flora-Scan) for detection of bacteria in the bloodstream...
November 14, 2017: Annals of Nutrition & Metabolism
https://www.readbyqxmd.com/read/29133420/resident-macrophages-of-pancreatic-islets-have-a-seminal-role-in-the-initiation-of-autoimmune-diabetes-of-nod-mice
#5
Javier A Carrero, Derrick P McCarthy, Stephen T Ferris, Xiaoxiao Wan, Hao Hu, Bernd H Zinselmeyer, Anthony N Vomund, Emil R Unanue
Treatment of C57BL/6 or NOD mice with a monoclonal antibody to the CSF-1 receptor resulted in depletion of the resident macrophages of pancreatic islets of Langerhans that lasted for several weeks. Depletion of macrophages in C57BL/6 mice did not affect multiple parameters of islet function, including glucose response, insulin content, and transcriptional profile. In NOD mice depleted of islet-resident macrophages starting at 3 wk of age, several changes occurred: (i) the early entrance of CD4 T cells and dendritic cells into pancreatic islets was reduced, (ii) presentation of insulin epitopes by dispersed islet cells to T cells was impaired, and (iii) the development of autoimmune diabetes was significantly reduced...
November 13, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29123529/t-cell-mediated-chronic-inflammatory-diseases-are-candidates-for-therapeutic-tolerance-induction-with-heat-shock-proteins
#6
REVIEW
Ariana Barbera Betancourt, Qingkang Lyu, Femke Broere, Alice Sijts, Victor P M G Rutten, Willem van Eden
Failing immunological tolerance for critical self-antigens is the problem underlying most chronic inflammatory diseases of humans. Despite the success of novel immunosuppressive biological drugs, the so-called biologics, in the treatment of diseases such rheumatoid arthritis (RA) and type 1 diabetes, none of these approaches does lead to a permanent state of medicine free disease remission. Therefore, there is a need for therapies that restore physiological mechanisms of self-tolerance. Heat shock proteins (HSPs) have shown disease suppressive activities in many models of experimental autoimmune diseases through the induction of regulatory T cells (Tregs)...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29123516/avidity-and-bystander-suppressive-capacity-of-human-regulatory-t-cells-expressing-de-novo-autoreactive-t-cell-receptors-in-type-1-diabetes
#7
Wen-I Yeh, Howard R Seay, Brittney Newby, Amanda L Posgai, Filipa Botelho Moniz, Aaron Michels, Clayton E Mathews, Jeffrey A Bluestone, Todd M Brusko
The ability to alter antigen specificity by T-cell receptor (TCR) or chimeric antigen receptor (CAR) gene transfer has facilitated personalized cellular immune therapies in cancer. Inversely, this approach can be harnessed in autoimmune settings to attenuate inflammation by redirecting the specificity of regulatory T cells (Tregs). Herein, we demonstrate efficient protocols for lentiviral gene transfer of TCRs that recognize type 1 diabetes-related autoantigens with the goal of tissue-targeted induction of antigen-specific tolerance to halt β-cell destruction...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29108826/physical-activity-and-autoimmune-diseases-get-moving-and-manage-the-disease
#8
REVIEW
Kassem Sharif, Abdulla Watad, Nicola Luigi Bragazzi, Micheal Lichtbroun, Howard Amital, Yehuda Shoenfeld
Physical activity, by definition, is any skeletal muscle body movement that results in energy expenditure. In the last few decades, a plethora of scientific evidences have accumulated and confirmed the beneficial role of physical activity as a modifiable risk factor for a wide variety of chronic diseases including cardiovascular diseases (CVDs), diabetes mellitus and cancer, among others. Autoimmune diseases are a heterogeneous group of chronic diseases, which occur secondary to loss of self-antigen tolerance...
November 3, 2017: Autoimmunity Reviews
https://www.readbyqxmd.com/read/29102469/a-sweet-deal-for-diabetes
#9
Matteo Villa, Jing Qiu, Erika L Pearce
Sugars have pathogenic roles in diabetes. In Nature Medicine, Zhang et al. revisit this dogma and show that mannose induces the generation of regulatory T (Treg) cells. The immunoregulatory effect of mannose not only prevented the onset of autoimmune diabetes but also blocked disease progression in new-onset diabetic mice.
November 1, 2017: Trends in Endocrinology and Metabolism: TEM
https://www.readbyqxmd.com/read/29097999/clostridium-butyricum-cgmcc0313-1-protects-against-autoimmune-diabetes-by-modulating-intestinal-immune-homeostasis-and-inducing-pancreatic-regulatory-t-cells
#10
Lingling Jia, Kai Shan, Li-Long Pan, Ninghan Feng, Zhuwu Lv, Yajun Sun, Jiahong Li, Chengfei Wu, Hao Zhang, Wei Chen, Julien Diana, Jia Sun, Yong Q Chen
Recent evidence indicates that indigenous Clostridium species induce colonic regulatory T cells (Tregs), and gut lymphocytes are able to migrate to pancreatic islets in an inflammatory environment. Thus, we speculate that supplementation with the well-characterized probiotics Clostridium butyricum CGMCC0313.1 (CB0313.1) may induce pancreatic Tregs and consequently inhibit the diabetes incidence in non-obese diabetic (NOD) mice. CB0313.1 was administered daily to female NOD mice from 3 to 45 weeks of age. The control group received an equal volume of sterile water...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29092650/phenotypic-characterization-of-regulatory-t-cells-populations-in-maternal-blood-cord-blood-and-placenta-from-diabetic-mothers
#11
A A Queiroz, E L França, C C P Hara, M S Honorio, D L G Fagundes, I M P B Calderon, A C Honorio-França
Changes in regulatory T cells (Treg) in peripheral blood are associated with a number of pathologies, including diabetes. However, the immunological responses of pregnant diabetic women remain scarcely known, and the effects of Treg cells in these patients have yet to be investigated. The present study characterized the expression of regulatory T cells in the maternal blood, cord blood and placenta of diabetic pregnant women. The women were divided according to glycemic status into a nondiabetic (ND; N = 20) or type 2 diabetic (T2DM; N = 20) group...
November 1, 2017: Journal of Maternal-fetal & Neonatal Medicine
https://www.readbyqxmd.com/read/29078283/humanized-mouse-model-supports-development-function-and-tissue-residency-of-human-natural-killer-cells
#12
Dietmar Herndler-Brandstetter, Liang Shan, Yi Yao, Carmen Stecher, Valerie Plajer, Melanie Lietzenmayer, Till Strowig, Marcel R de Zoete, Noah W Palm, Jie Chen, Catherine A Blish, Davor Frleta, Cagan Gurer, Lynn E Macdonald, Andrew J Murphy, George D Yancopoulos, Ruth R Montgomery, Richard A Flavell
Immunodeficient mice reconstituted with a human immune system represent a promising tool for translational research as they may allow modeling and therapy of human diseases in vivo. However, insufficient development and function of human natural killer (NK) cells and T cell subsets limit the applicability of humanized mice for studying cancer biology and therapy. Here, we describe a human interleukin 15 (IL15) and human signal regulatory protein alpha (SIRPA) knock-in mouse on a Rag2(-/-)Il2rg(-/-) background (SRG-15)...
October 25, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29075262/clinical-tolerogenic-dendritic-cells-exploring-therapeutic-impact-on-human-autoimmune-disease
#13
REVIEW
Brett Eugene Phillips, Yesica Garciafigueroa, Massimo Trucco, Nick Giannoukakis
Tolerogenic dendritic cell (tDC)-based clinical trials for the treatment of autoimmune diseases are now a reality. Clinical trials are currently exploring the effectiveness of tDC to treat autoimmune diseases of type 1 diabetes mellitus, rheumatoid arthritis, multiple sclerosis (MS), and Crohn's disease. This review will address tDC employed in current clinical trials, focusing on cell characteristics, mechanisms of action, and clinical findings. To date, the publicly reported human trials using tDC indicate that regulatory lymphocytes (largely Foxp3+ T-regulatory cell and, in one trial, B-regulatory cells) are, for the most part, increased in frequency in the circulation...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29066174/attenuation-of-cd4-cd25-regulatory-t-cells-in-the-tumor-microenvironment-by-metformin-a-type-2-diabetes-drug
#14
Yuki Kunisada, Shingo Eikawa, Nahoko Tomonobu, Shohei Domae, Takenori Uehara, Shohei Hori, Yukihiro Furusawa, Koji Hase, Akira Sasaki, Heiichiro Udono
CD4(+)CD25(+) regulatory T cells (Treg), an essential subset for preventing autoimmune diseases, is implicated as a negative regulator in anti-tumor immunity. We found that metformin (Met) reduced tumor-infiltrating Treg (Ti-Treg), particularly the terminally-differentiated CD103(+)KLRG1(+) population, and also decreased effector molecules such as CTLA4 and IL-10. Met inhibits the differentiation of naïve CD4(+) T cells into inducible Treg (iTreg) by reducing forkhead box P3 (Foxp3) protein, caused by mTORC1 activation that was determined by the elevation of phosphorylated S6 (pS6), a downstream molecule of mTORC1...
November 2017: EBioMedicine
https://www.readbyqxmd.com/read/29062902/the-interplay-between-th17-and-t-regulatory-responses-as-well-as-adipokines-in-the-progression-of-non-alcoholic-fatty-liver-disease
#15
REVIEW
Magdalena Świderska, Jerzy Jaroszewicz, Agnieszka Stawicka, Anna Parfieniuk-Kowerda, Adrian Chabowski, Robert Flisiak
Non-alcoholic fatty liver disease (NAFLD) is a chronic progressive liver disease, coupled with metabolic syndrome, which may progress to non-alcoholic steatohepatitis (NASH). Diabetes, obesity, hypertension, hypercholesterolemia, and hypertriglyceridemia are considered to be the most common causes leading to the incidence of NAFLD. It is assumed that the accumulation of lipid deposits in hepatocytes leads to production of proinflammatory cytokines that triggers the development of liver inflammation. Regulatory T cells (Tregs) play a critical role in regulating inflammatory processes in NASH, while T helper type 17 (Th17) might functionally oppose Treg-mediated responses...
September 2017: Clin Exp Hepatol
https://www.readbyqxmd.com/read/29055004/stat4-regulates-the-cd8-regulatory-t-cell-t-follicular-helper-cell-axis-and-promotes-atherogenesis-in-insulin-resistant-ldlr-mice
#16
Parésa L Taghavie-Moghadam, Tayab C Waseem, Julian Hattler, Lindsey M Glenn, Anca D Dobrian, Mark H Kaplan, Yi Yang, Roza Nurieva, Jerry L Nadler, Elena V Galkina
The metabolic syndrome and diabetic conditions support atherosclerosis, but the exact mechanisms for accelerated atherogenesis remain unclear. Although the proinflammatory role of STAT4 in atherosclerosis and diet-induced insulin resistance (IR) was recently established, the impact of STAT4 on atherogenesis in conditions of IR is not known. In this study, we generated Stat4(-/-)Ldlr(-/-) mice that were fed a diabetogenic diet with added cholesterol (DDC). DDC-fed Stat4(-/-)Ldlr(-/-) mice demonstrated improved glucose tolerance, insulin sensitivity, and a 36% reduction in atherosclerosis compared with Ldlr(-/-) controls...
November 15, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29055002/transient-baff-blockade-inhibits-type-1-diabetes-development-in-nonobese-diabetic-mice-by-enriching-immunoregulatory-b-lymphocytes-sensitive-to-deletion-by-anti-cd20-cotherapy
#17
Qiming Wang, Jeremy J Racine, Jeremy J Ratiu, Shu Wang, Rachel Ettinger, Clive Wasserfall, Mark A Atkinson, David V Serreze
In NOD mice and also likely humans, B lymphocytes play an important role as APC-expanding autoreactive T cell responses ultimately causing type 1 diabetes (T1D). Currently, humans at high future T1D risk can only be identified at late prodromal stages of disease indicated by markers such as insulin autoantibodies. When commenced in already insulin autoantibody(+) NOD mice, continuous BAFFR-Fc treatment alone or in combination with anti-CD20 (designated combo therapy) inhibited T1D development. Despite eliciting broader B lymphocyte depletion, continuous combo therapy afforded no greater T1D protection than did BAFFR-Fc alone...
October 20, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29051105/nicotine-and-autoimmunity-the-lotus-flower-in-tobacco
#18
REVIEW
João Pedro Gomes, Abdulla Watad, Yehuda Shoenfeld
Nicotine, the major component of cigarettes, has demonstrated conflicting impact on the immune system: some authors suggest that increases pro-inflammatory cytokines and provokes cellular apoptosis of neutrophils, releasing intracellular components that act as auto-antigens; others claimed that nicotine has a protective and anti-inflammatory effects, especially by binding to α7 subunit of nicotinic acetylcholine receptors. The cholinergic pathway contributes to an anti-inflammatory environment characterized by increasing T regulatory cells response, down-regulating of pro-inflammatory cytokines and a pro-inflammatory cells apoptosis...
October 16, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/29034636/-high-dose-heat-shock-protein-gp96-immunization-prevents-type-1-diabetes-via-inducing-regulatory-t-cells
#19
Mi Chen, Xinghui Li, Huaguo Zheng, Songdong Meng
Type 1 diabetes (T1D), the most prevalent human autoimmune disease, occurs in genetically susceptible individuals. Regulatory T cells (Tregs) are defective in T1D setting. Therefore, efforts to repair or restore Tregs in T1D may prevent or reverse this autoimmune disease. Here, we studied the potential role of rgp96 in preventing T1D, using non-obese diabetic (NOD) mice as an animal model. High-dose rgp96 immunization elicited efficient protection of mice against T1D, as evidenced by stable blood glucose, decreased disease incidence...
December 25, 2016: Sheng Wu Gong Cheng Xue Bao, Chinese Journal of Biotechnology
https://www.readbyqxmd.com/read/29033948/unique-features-of-pancreatic-resident-regulatory-t-cells-in-autoimmune-type-1-diabetes
#20
REVIEW
Jingli Lu, Chaoqi Zhang, Lifeng Li, Wenhua Xue, Chengliang Zhang, Xiaojian Zhang
Recent progress in regulatory T cells (Tregs) biology emphasizes the importance of understanding tissue-resident Tregs in response to tissue-specific environment. Now, emerging evidence suggests that pancreatic-resident forkhead box P3(+) Tregs have distinguishable effects on the suppression of over-exuberant immune responses in autoimmune type 1 diabetes (T1D). Thus, there is growing interest in elucidating the role of pancreatic-resident Tregs that function and evolve in the local environment. In this review, we discuss the phenotype and function of Tregs residing in pancreatic tissues and pancreatic lymph nodes, with emphasis on the unique subpopulations of Tregs that control the disease progression in the context of T1D...
2017: Frontiers in Immunology
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