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Autoimmunity pp 169–180Cite as

Murine Models of Lupus Induced by Hypomethylated T Cells (DNA Hypomethylation and Lupus…)

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Part of the book series: Methods in Molecular Biology ((MIMB,volume 900))

Abstract

CD4+ T cell DNA hypomethylation may contribute to the development of drug induced and idiopathic human lupus. Inhibiting DNA methylation in mature CD4+ T cells causes MHC-specific autoreactivity in vitro. The lupus-inducing drugs hydralazine and procainamide also inhibit T cell DNA methylation and induce autoreactivity, and T cells from patients with active lupus have hypomethylated DNA and a similarly autoreactive T cell subset. Further, T cells treated with DNA methylation inhibitors demethylate the same sequences that demethylate in T cells from patients with active lupus. The pathologic significance of the autoreactivity induced by inhibiting T cell DNA methylation has been tested by treating murine T cells in vitro with drugs which modify DNA methylation, then injecting the cells into syngeneic female mice. Mice receiving CD4+ T cells demethylated by a variety of agents including procainamide and hydralazine develop a lupus-like disease. Further, transgenic mice with an inducible T cell DNA methylation defect also develop lupus-like autoimmunity. This chapter describes the protocols for inducing autoreactivity in murine T cells in vitro and for inducing autoimmunity in vivo using an adoptive transfer approach or transgenic animal models.

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Authors and Affiliations

  1. University of Michigan and the Ann Arbor Veteran’s Affairs Hospital, Ann Arbor, MI, USA

    Bruce Richardson & Amr H. Sawalha

  2. Ann Arbor Veteran’s Affairs Hospital, University of Michigan, Ann Arbor, MI, USA

    Donna Ray & Raymond Yung

Authors
  1. Bruce Richardson
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  2. Amr H. Sawalha
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  3. Donna Ray
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  4. Raymond Yung
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Corresponding author

Correspondence to Bruce Richardson .

Editor information

Editors and Affiliations

  1. College of Medicine, Division of Rheumatology, State University of New York, UMU, East Adams St. 750, Syracuse, 13210, New York, USA

    Andras Perl

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Richardson, B., Sawalha, A.H., Ray, D., Yung, R. (2012). Murine Models of Lupus Induced by Hypomethylated T Cells (DNA Hypomethylation and Lupus…). In: Perl, A. (eds) Autoimmunity. Methods in Molecular Biology, vol 900. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-60761-720-4_8

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  • DOI: https://doi.org/10.1007/978-1-60761-720-4_8

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  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-60761-719-8

  • Online ISBN: 978-1-60761-720-4

  • eBook Packages: Springer Protocols

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