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Impaired DNA Methylation in Lupus T Cells

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Lupus

Part of the book series: Contemporary Immunology ((CONTIM))

Abstract

Although lupus is commonly thought of as a B-cell disease, evidence from murine models of lupus-like syndromes and our understanding of how T cells coordinate the overall immune response suggest that T cells play a fundamental role in this disorder. Our group has developed a model that directly implicates T cells in the initiation of drug-induced and idiopathic lupus, and suggests molecular mechanisms relevant to this process. These studies derive from experiments aimed at determining the importance of DNA methylation in the regulation of T-cell function and gene expression. One particularly interesting outcome of these experiments is that hypomethylated CD4+ cells are no longer dependent on antigen for activation, and respond to antigen-presenting cells (APCs) lacking specific antigen, thus demonstrating characteristics of autoreactivity. We have used this observation to develop a working model for the study of both idiopathic and drug-induced lupus, in which methylation changes in the promoter sequences of critical genes lead to autoreactivity, and the autoreactive T cells then induce an autoimmune disease. This chapter reviews the current concepts regarding DNA methylation and its role in gene regulation, and relates this information to our model of T-cell—induced lupus-like disease. Finally, this chapter describes our current work for consideration as an area of research to be pursued to understand fully the molecular events initiating lupus.

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Authors
  1. Jeannine M. Scott
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  2. Bruce C. Richardson
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Editors and Affiliations

  1. Section on Rheumatology, Department of Internal Medicine, The Wake Forest University School of Medicine, Winston-Salem, NC, USA

    Gary M. Kammer MD

  2. Division of Rheumatology and Immunology, Uniformed Services University of Health Sciences, Bethesda, MD, USA

    George C. Tsokos MD

  3. Department of Clinical Physiology, Walter Reed Army Institute of Research, Washington, DC, USA

    George C. Tsokos MD

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© 1999 Springer Science+Business Media New York

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Scott, J.M., Richardson, B.C. (1999). Impaired DNA Methylation in Lupus T Cells. In: Kammer, G.M., Tsokos, G.C. (eds) Lupus. Contemporary Immunology. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-59259-703-1_17

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  • DOI: https://doi.org/10.1007/978-1-59259-703-1_17

  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-4757-5686-9

  • Online ISBN: 978-1-59259-703-1

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