Articles That Use the Category Name:

Species and Cell Types / Human / Immune System / Lymphocyte / Regulatory T Cell


MicroRNAs Regulate Immune System Via Multiple Targets

Abstract: MicroRNAs (miRNAs) represent the most abundant class of regulators of gene expression. Each miRNA may suppress multiple mRNA targets, while one mRNA can be targeted by many miRNAs for precise control of a wide range of cellular processes. The important role of miRNAs in the immune system is highlighted by the conditional Dicer knockout mouse, which exhibited profound aberrant development and function of immune cells. One particular miRNA, miR-155, is highly expressed and plays important role in lymphocytes. In this review we focused on the role of miRNA, especially miR-155, via their predicted and known mRNA targets in innate and adaptive immunity. Finally, we discussed the potential of miRNAs as novel targets for the diagnosis and therapy of immune system diseases. ... Read more

Mesenchymal Stem Cell-Based Therapy for Type 1 Diabetes

Abstract: Diabetes has increasingly become a worldwide health problem, causing huge burden on healthcare system and economy. Type 1 diabetes (T1D), traditionally termed "juvenile diabetes" because of an early onset age, is affecting 5~10% of total diabetic population. Insulin injection, the predominant treatment for T1D, is effective to ameliorate the hyperglycemia but incompetent to relieve the autoimmunity and to regenerate lost islets. Islet transplantation, an experimental treatment for T1D, also suffers from limited supply of human islets and poor immunosuppression. The recent progress in regenerative medicine, especially stem cell therapy, has suggested several novel and potential cures for T1D. Mesenchymal stem cell (MSC) based cell therapy is among one of them. MSCs are a type of adult stem cells residing in bone marrow, adipose tissue, umbilical cord blood, and many other tissues. MSCs, with self-renewal potential and transdifferentiation capability, can be expanded in vitro and directed to various cell lineages with relatively less efforts. MSCs have well-characterized hypoimmunogenicity and immunomodulatory effect. All these features make MSCs attractive for treating T1D. Here, we review the properties of MSCs and some of the recent progress using MSCs as a new therapeutic in the treatment of T1D. We also discuss the strength and limitations of using MSC therapy in human trials. ... Read more

Tolerance Induction in Hemophilia A Animal Models: Battling Inhibitors with Antigen-specific Immunotherapies

Abstract: Hemophilia A is an X-linked recessive bleeding disorder due to either a lack of or greatly reduced activity in the blood coagulation protein factor VIII (FVIII), due to mutations in the F8 gene. This poses significant challenges for FVIII replacement therapy since hemophilic patients are not immunologically tolerant to the protein. Thus, a proportion of patients who receive plasma-derived or recombinant FVIII replacement therapy develop anti FVIII neutralizing antibodies, known as "inhibitors." These patients require long-term regimens of high dose FVIII administration, which has varying success rates and prohibitive costs. Therefore, therapeutics for tolerance induction in such patients with inhibitors are desired. In this review, we address the current progress of immunotherapies for inducing FVIII specific tolerance in animal models of hemophilia A. Specifically we discuss the beneficial effects of B-cell depletion on immune tolerance induction (ITI), B-cell mediated gene therapy, antigen-coupled lymphocyte therapy, and regulatory T-cell epitopes (Tregitopes). ... Read more

Advances in Immune Regulation in Transplantation

Abstract: In the last three decades, we have observed a substantial progress in the organ and cell transplantation. New immune suppressive agents including calcineurin blockers and mTOR inhibitors improved transplantation outcome, but two key problems -- rejection of transplanted organs and graft versus host disease (GVHD) -- continue to be main obstacles after transplantation. Immune response is regulated with coordination of a varying number of cells. T regulatory cells orchestrate other cell responses and eventually limit immune activation and induce immune tolerance. Stimulation of negative costimulatory molecules and adoptive transfer of immunosuppressive cells including regulatory cells are promising therapies that would improve outcome of patients with organ or cell transplantation. ... Read more

Elusive Alzheimer's Disease: Can Immune Signatures Help Our Understanding of This Challenging Disease? Part 2: New Immune Paradigm

Abstract: Alzheimer's disease (AD) is the most common form of dementia. Its most important pathological hallmarks are profound neuronal loss, presence of intracellular neurofibrillary tangles, and extracellular deposition of beta-amyloid protein (Aβ) as beta-amyloid plaques. One of the most important risk factors for AD is age and with the increase of life-expectancy AD has become the most common form of dementia. The current "Holy Grail" is to be able to diagnose variants of AD before they manifest clinically and before irreparable brain damage is done. To be able to do so, we need robust and reliable biomarkers which reflect the pathogenesis of AD. This is essential because such biomarkers might indicate pathways that could be targeted for interventions aiming at disease prevention or amelioration. Although much attention has been focused on Aβ in this respect, it may not be as attractive a target as thought if current doubts concerning its causative role are substantiated. This review will be in two parts, the first part dealt with the current clinical knowledge and the questions raised by the Aβ cascade hypothesis in the pathogenesis of AD and this second part aims to synthesize our current knowledge and new data suggesting how immunity may contribute to the development of AD and may itself be targeted in future treatments. ... Read more

Does the Gut Microbiota Trigger Hashimoto's Thyroiditis?

Abstract: Hashimoto's thyroiditis is an organ-specific autoimmune disease in which both genetic predisposition and environmental factors serve as the trigger of the disease. A growing body of evidence suggests involvement of viral infection in the development of Hashimoto's thyroiditis. However, not only pathogenic microorganisms but also non-pathogenic commensal microorganisms induce proinflammatory or regulatory immune responses within the host. In accordance, series of studies indicate a critical role of intestinal commensal microbiota in the development of autoimmune diseases including inflammatory bowel diseases, type 1 diabetes, rheumatoid arthritis, and multiple sclerosis. In contrast, the role of the gut and indigenous microorganisms in Hashimoto's thyroiditis has received little attention. Whereas activation of innate pattern recognition receptors such as Toll-like receptors and disturbed intestinal epithelial barrier may contribute to thyroiditis development, only a few studies have addressed a link between the gut and Hashimoto's thyroiditis and provided just indirect and weak evidence for such a link. Despite this unsatisfactory situation, we here focus on the possible interaction between the gut and thyroid autoimmunity. Further studies are clearly needed to test the hypothesis that the gut commensal microflora represents an important environmental factor triggering Hashimoto's thyroiditis. ... Read more

Advances in Immunotherapy for Food Allergy

Abstract: Food allergy is a life-threatening allergic disease that is increasing in prevalence with no approved curative therapy. Standard treatment of food allergy is limited to avoidance of the allergen and supportive management of allergic symptoms and anaphylaxis. Current research, however, has been focused on developing therapy that can modify the allergic immune response in both allergen-specific and non-specific methods. This review will provide an overview of these methods including oral immunotherapy, sublingual immunotherapy, epicutaneous immunotherapy, modified food protein vaccines, anti-IgE monoclonal antibody adjuvant therapy, Chinese herbs, and helminth therapy. ... Read more

Advances in Therapeutic Vaccines for Pancreatic Cancer

Abstract: Pancreatic cancer is one of the most difficult-to-treat cancers. Despite surgical resection, radiation and/or chemotherapy, greater than 94% of people with pancreatic cancer do not survive beyond 5 years. In fact, median survival after diagnosis of metastatic pancreatic cancer is 4.5 months. The majority of patients are diagnosed with nonresectable, metastatic disease, and chemotherapy only extends their median survival by less than 2 months with only 18% of those treated surviving beyond 1 year. Despite the severity of their disease, most patients exhibit tumor specific cellular immunity to their pancreatic cancer antigens. Obviously their immunity is ineffective in preventing tumor growth. Recent studies have demonstrated that the tumor microenvironment may hold the key to determining the nature of the tumors' ability to escape from immune attack. Preliminary clinical trials have suggested that blocking these escape mechanisms may result in survival benefit to the patients, and phase I and II clinical trials with tumor vaccines have led to some survival benefits. Perhaps combining therapies directed against immune escape mechanisms with tumor vaccines will result in even greater survival benefit for patients with pancreatic cancer. While therapeutic vaccines for pancreatic cancers have been reviewed previously (Plate, 2011), updates on recent preliminary reports of two clinical vaccine trials are worthy of our attention. ... Read more

Vitamin D Supplementation, Moderate Sun Exposure, and Control of Immune Diseases

Abstract: There is considerable debate about the benefits of vitamin D supplementation for multiple sclerosis, allergic asthma, and type 1 diabetes. This has been driven mainly by observational studies linking vitamin D deficiency and insufficiency with increased prevalence of autoimmune and other diseases driven by immune processes. Randomized controlled trials of vitamin D supplementation to treat these (and other) diseases have been disappointing. This review examines the evidence that circulating vitamin D levels provide a surrogate measure of sun exposure and that it is the other molecules and pathways induced by sun exposure, rather than vitamin D-driven processes, that explain many of the benefits often attributed to vitamin D. ... Read more

miRNAs at the Crossroad Between Hematopoietic Malignancies and Autoimmune Pathogenesis

Abstract: The study of microRNA (miRNA) regulation in the pathogenesis of autoimmune diseases and hematopoietic malignancies provides new understanding of the mechanisms of disease and is currently the focus of many researchers in the field. Autoimmune disorders and cancers of immune system comprise a wide range of genetically complex diseases that share certain aspects of dysregulated genetic networks, most notably deactivation of apoptosis. miRNA mechanisms control gene expression at the post-transcriptional level, linking mRNA processing and gene function. Considerable amount of data have been accumulated that indicate that the alteration of miRNA expression closely mirrors the development of immune system diseases and is likely to play a role in their pathogenesis. However, a knowledge gap remains in our understanding of how miRNA dysregulation and the specific effects of miRNAs on target gene expression underlay the disease phenotype. Here we review a number of studies describing miRNA alterations in autoimmune diseases and hematopoietic cancers and discuss potential miRNA-regulated mechanisms that differentially influence the development of autoimmunity as compared to cancer progression. ... Read more

Close
Close
E-mail It
Close