Abstract: Systemic lupus erythematosus (SLE) is a common autoimmune disease with unclear etiology. Treatments for it often provide inadequate control of disease activity or are limited by side effects. Recent studies have shown that rapamycin can be an effective treatment in both murine lupus models and human SLE. We demonstrated that rapamycin could directly alter molecular abnormalities in SLE T cells related to calcium signaling but not mitochondrial function. However, in light of increased knowledge of the role of mammalian target of rapamycin (mTOR) signaling throughout the immune system, several other potential sites of rapamycin action have been revealed. Specifically, mTOR regulates the production of interferon-α and the maintenance of immune tolerance at the level of the regulatory T cell and the dendritic cell, and can promote Th1 versus Th2 immune responses. Thus mTOR offers a window into diverse facets of SLE pathogenesis as well as a potentially unifying narrative in our understanding of diverse facets of the disease. ... Read more

Abstract: Infectious agents contribute to the environmental factors involved in the development of autoimmune diseases possibly through molecular mimicry mechanisms. Hence, it is feasible that vaccinations may also contribute to the mosaic of autoimmunity. Evidence for the association of vaccinations and the development of these diseases is presented in this review. Infrequently reported post-vaccination autoimmune diseases include systemic lupus erythematosus, rheumatoid arthritis, inflammatory myopathies, multiple sclerosis, Guillain-Barré syndrome, and vasculitis. In addition, we will discuss macrophagic myofasciitis, aluminum containing vaccines, and the recent evidence for autoimmunity following human papilloma virus vaccine. ... Read more

Abstract: In this review, I outline a current view of how T lymphocytes use extracellular signals to decide between activation and tolerance, and how the tolerant state is established and maintained at the molecular level. This decision is made by a series of intracellular proteins that actively oppose the induction of effector genes, and are inactivated by signals from costimulatory and/or growth factor receptors. ... Read more

Abstract: Type 1 diabetes (T1D) is an autoimmune disease in which the patient's immune system recognizes their pancreatic islet insulin-producing cells and destroys them. To cure T1D in a comprehensive manner, not only must the islet cells be replaced, the patient's immune system must also be properly regulated mostly in the form of suppression. Blood-derived new stem cells have shown promise in both aspects of this treatment. ... Read more

Abstract: The evolution of the immune system has provided a multilevel system that interconnects the innate and adaptive immune systems to serve at least three central purposes: the defense from microbial pathogens, the capacity for discrimination of self- from non-self necessary for the prevention of autoimmune disease, and essential effector roles in wound repair and tissue remodeling. In recent studies, we have elucidated an unsuspected role for a class of naturally occurring autoreactive antibodies from the most primitive tier of B lymphocytes, which regulates fundamental functions of the innate immune system. Our findings also throw light onto long unresolved mysteries regarding the origins of the earliest waves of B lymphocyte development. ... Read more

Abstract: Rasmussen encephalitis (RE) is characterized by chronic inflammation of one cerebral hemisphere which causes intractable epileptic seizures and progressive neurological deficits. Since antiepileptic pharmacotherapy is often ineffective the traditional therapy for Rasmussen encephalitis is hemispherectomy in one of its modern variants which renders the patient seizure free but leads to a severe deficit. To escape this dilemma, immunomodulatory therapeutic approaches such as rituximab, a monoclonal anti-CD20 antibody, offer an alternative and bear promising therapeutic potentials in Rasmussen encephalitis. ... Read more

Abstract: Interleukin-21 (IL-21), a cytokine produced by activated CD4+ T cells, activated natural killer T cells, and T follicular cells, has been reported to play a crucial role in the tissue-damaging T cell response in various organs, such as gut, skin, pancreas, and joints. This pathogenic effect is strictly linked to the ability of IL-21 to enhance the functional activities of multiple immune and non-immune cells. Consistently, studies from various laboratories have shown that blockade of IL-21 limits the progression of T cell-mediated inflammatory diseases in mice. Here we review the present knowledge on the expression and role of IL-21 in T cell-mediated pathologies. ... Read more

Abstract: Ghrelin is a recently identified gastric hormone that displays strong growth hormone (GH) releasing activity mediated by the GH secretagogue receptor (GHS-R). While this unique endogenous peptide participates in the regulation of energy homeostasis, increases food intake, and decreases energy expenditure, its ability to modulate immune regulation is another important feature. Here we discuss the effect of ghrelin on the immune system. Ghrelin was initially reported as an immune enhancing factor. More recently, however, the immunosuppressive effects of ghrelin have been found in several animal models including bowel disease, arthritis, and sepsis and endotoxemia. We recently demonstrated that exogenous administration of ghrelin suppressed experimental autoimmune encephalomyelitis, an animal model of multiple sclerosis in association with the reduction of pro-inflammatory cytokines in microglia. These results shed light on the new role of ghrelin in the regulation of disorders that pro-inflammatory cytokines contribute to the pathogenesis such as neuroinflammatory and mental diseases. ... Read more

Abstract: CD4⁺CD25⁺Foxp3⁺ regulatory T (Treg) cells suppress the proliferation and release of cytokines in several subsets of immune cells. By doing so and by maintaining immune tolerance in peripheral tissues, Treg cells contribute to avert autoimmunity. Many studies have investigated how Treg cells operate in autoimmune diseases, and which cellular and molecular pathways are targeted by Treg cells. This review provides an update on the activities of Treg cells in systemic lupus erythematosus (SLE), an autoimmune disease characterized by the presence of hyperactive immune cells and aberrant antibody responses to multiple nuclear and cytoplasmic antigens. ... Read more

Abstract: Historically atherosclerosis has been viewed as a disease associated with dyslipidemia because many studies (e.g., Framingham study) have demonstrated that dyslipidemia is clearly a risk factor for the disease and lipid-lowering statin therapies have proven to be highly effective in reducing the cardiovascular events and improving the quality of life for patients with coronary heart disease all over the world. Over the last decade, both preclinical and clinical research has provided multiple lines of unequivocal evidence that inflammation and immune response are integral components of the pathogenesis for atherosclerosis. In this article, both clinical and preclinical evidence in support of atherosclerosis as an inflammatory disease will be reviewed. Evidence in support of atherosclerosis as an autoimmune disease will also be presented. Furthermore, opportunities for translating the newly gained knowledge of atherosclerosis as an inflammatory/autoimmune disease into novel diagnostic and therapeutic modalities will be discussed along with challenges in developing these modalities. ... Read more