Rheumatoid arthritis (RA) is a chronic systemic inflammatory disease of unknown etiology that primarily affects the synovial membranes of multiple joints and frequently accompanies extra-articular lesions [1, 2]. Both genetic and environmental factors contribute to the development of RA [1, 2]. Recent studies have facilitated our understanding of the process of chronic joint inflammation, in particular the roles of proinflammatory cytokines (such as TNF-a, IL-1, and IL-6) . Neutralization of these cytokines or blockade of their action can indeed halt the progression of the disease [4, 5]. It is still obscure, however, how RA is triggered in the first place. RA has been suspected to be autoimmune in etiology because of the presence of autoantibodies, such as rheumatoid factors (RF) , association with particular haplotypes of the HLA Class II gene [6, 7], occasional familial clustering with other autoimmune diseases [8, 9], infiltration of self-reactive CD4+ T-cells in synovial inflammation (synovitis), and successful induction of arthritis in animals by immunization with self-constituents, such as type II collagen, in potent adjuvant . There are also many reports that environmental agents, especially viruses, may directly affect the joint, causing chronic joint inflammation . Fundamental questions in understanding the etiology of RA would therefore be how synovitis is initiated, in particular whether it is an autoimmunity mediated by self-reactive CD4+ T-cells; if this is the case, how then arthritogenic self-reactive CD4+ T-cells are generated and activated; and how genetic and environmental factors contribute to their generation and activation. Animal models of RA, in particular spontaneous models, are instrumental in addressing these questions. We have recently established a mouse strain that spontaneously develops CD4+ T-cell-mediated chronic autoimmune arthritis immunopathologically resembling human RA . The primary cause of the disease is a point mutation of the gene encoding ZAP-70, a key signal transduction molecule in T-cells . In this article, we discuss how this mono-genetic defect in T-cells, not in the joint, leads to the generation and activation of arthritogenic self-reactive CD4+ T-cells, what roles environmental factors play in the development of arthritis in the presence of this genetic abnormality, and how the findings in this model could be extended to our understanding of the etiology of human RA.
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Thank you for deciding to learn more about the disorder, Osteoarthritis. Inside these pages, you will learn what it is, who is most at risk for developing it, what causes it, and some treatment plans to help those that do have it feel better. While there is no definitive “cure” for Osteoarthritis, there are ways in which individuals can improve their quality of life and change the discomfort level to one that can be tolerated on a daily basis.