Immuno- and genetic therapy in autoimmune diseases

Abstract

Animal models of autoimmune disease have been developed that mimic some aspects of the pathophysiology of human disease. These models have increased our understanding of possible mechanisms of pathogenesis at the molecular and cellular level and have been important in the testing, development and validation of new immunotherapies. The susceptibility to develop disease in the majority of these models is polygenic as is the case in humans. The exceptions to this rule are gene knock outs and transgenic models of particular genes which, in particular genetic backgrounds, have also contributed to the understanding of single gene function and their possible contribution to pathogenesis. Gene therapy approaches that target immune functions are being developed with encouraging results, despite the polygenic nature of these diseases. Basically this novel immuno-genetic therapy harnesses the knowledge of immunology with the myriad of biotechnological breakthroughs in vector design and delivery. Autoimmune disease is the result of genetic dysregulation which could be controlled by gene therapy. Here we summarize the genetic basis of these human diseases as well as some of the best characterized murine models. We discuss the strategies for their treatment using immunoand gene therapy. Genes and Immunity (2000) 1, 295-307.

Massive parallel gene expression profiling of RINm5F pancreatic islet β‐cells stimulated with interleukin‐1β

“…One of these, interleukin l p (IL-lp), is found in the circulation during immunoinflammatory conditions and is secreted in and around pancreatic islets of Langerhans in the early stages of type I diabetes. We and others have previously shown that low levels of IL-1 p inhibit glucose-stimulated insulin secretion by pancreatic islets and that high levels of the cytokine are uniquely toxic to pan-creatic p-cells (3)(4)(5)(6)(7)(8). The mechanism behind this is poorly understood (7,9), and increased knowledge of the spectrum of activities initiated by IL-1p in p-cells is a prerequisite for better understanding the susceptibility of p-cells to immunoinflammatory attacks and, hence, the molecular basis of type I diabetes.…”

Prevention of experimental autoimmune encephalomyelitis in DA rats by grafting primary skin fibroblasts engineered to express transforming growth factor-β1

“…Evidence from animal models supports convincingly that gene therapy can be an advantageous strategy in the treatment of inflammatory autoimmune disorders [19,20,25–28]. Recent reports of gene therapy in EAE have studied the use of hybridoma cells and CNS antigen‐specific T cells to deliver IL‐4 or TGF‐ β [19,26].…”

Efficient Production of Bioactive Insulin from Human Epidermal Keratinocytes and Tissue-Engineered Skin Substitutes: Implications for Treatment of Diabetes

“…On the other hand, islet transplantation suffers from scarcity of donors, the need for long-term immunosuppression, and short-term survival of transplanted cells because of recurrence of anti-islet cell autoimmunity. 4,5 Therefore, engineering alternative routes of physiologic insulin delivery is a major goal of diabetes research.…”