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Innate DNA and RNA Recognition pp 143–158Cite as

Evaluating the Role of Nucleic Acid Antigens in Murine Models of Systemic Lupus Erythematosus

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Part of the book series: Methods in Molecular Biology ((MIMB,volume 1169))

Abstract

Impaired apoptotic cell clearance is thought to contribute to the pathogenesis of systemic autoimmune disease, in particular systemic lupus erythematosus (SLE). Endogenous RNA- and DNA-containing autoantigens released from dying cells can engage Toll-like receptors (TLR) 7/8 and TLR9, respectively in a number of immune cell types, thereby promoting innate and adaptive immune responses. Mouse models of lupus reliably phenocopy many of the characteristic features of SLE in humans and these models have proved invaluable in defining disease mechanisms. TLR7 signaling is essential for the development of autoantibodies to RNA and RNA-associated proteins like Sm and RNP, while TLR9 signaling is important for the development of antibodies to DNA and chromatin. TLR7 deficiency ameliorates end-organ disease, but, surprisingly, TLR9 deficiency exacerbates disease, possibly as a result of TLR7 overactivity in TLR9-deficient mice. Deficiency of interferon regulatory factor 5 (IRF5) inhibits autoantibody production and ameliorates disease likely due to its role in both TLR7 and TLR9 signaling. In this report we describe methods to analyze two commonly used mouse models of SLE in which TLRs and/or IRF5 have been shown to play a role in disease pathogenesis.

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Acknowledgements

This work was supported by a grant from the Alliance for Lupus Research (I.R.R) and the following grants from the National Institutes of Health: P01 AR050256 (I.R.R), RO1 DK090558 (R.G.B.B), and a Research Training in Immunology T32 Grant AI007309-23 (A.A.W).

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Authors and Affiliations

  1. Renal Section, Department of Medicine, Boston University School of Medicine, Boston, MA, USA

    Amanda A. Watkins, Ramon G. B. Bonegio & Ian R. Rifkin

Authors
  1. Amanda A. Watkins
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  2. Ramon G. B. Bonegio
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  3. Ian R. Rifkin
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Correspondence to Ian R. Rifkin .

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Editors and Affiliations

  1. Ludwig Maximilians Universität München, Medizinische Klinik und Poliklinik IV, München, Germany

    Hans-Joachim Anders

  2. Helmholtz Zentrum München German Researc, Institute for Diabetes and Regeneration, Munich, Germany

    Adriana Migliorini

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Watkins, A.A., Bonegio, R.G.B., Rifkin, I.R. (2014). Evaluating the Role of Nucleic Acid Antigens in Murine Models of Systemic Lupus Erythematosus. In: Anders, HJ., Migliorini, A. (eds) Innate DNA and RNA Recognition. Methods in Molecular Biology, vol 1169. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-0882-0_14

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  • DOI: https://doi.org/10.1007/978-1-4939-0882-0_14

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  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-0881-3

  • Online ISBN: 978-1-4939-0882-0

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