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Intracellular Nucleic Acid Detection in Autoimmunity

Intracellular Nucleic Acid Detection in Autoimmunity Protective immune responses to viral infection are initiated by innate immune sensors that survey extracellular and intracellular space for foreign nucleic acids. The existence of these sensors raises fundamental questions about self/nonself discrimination because of the abundance of self-DNA and self-RNA that occupy these same compartments. Recent advances have revealed that enzymes that metabolize or modify endogenous nucleic acids are essential for preventing inappropriate activation of the innate antiviral response. In this review, we discuss rare human diseases caused by dysregulated nucleic acid sensing, focusing primarily on intracellular sensors of nucleic acids. We summarize lessons learned from these disorders, we rationalize the existence of these diseases in the context of evolution, and we propose that this framework may also apply to a number of more common autoimmune diseases for which the underlying genetics and mechanisms are not yet fully understood. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Annual Review of Immunology Annual Reviews

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Publisher
Annual Reviews
Copyright
Copyright © 2017 by Annual Reviews. All rights reserved
ISSN
0732-0582
eISSN
1545-3278
DOI
10.1146/annurev-immunol-051116-052331
pmid
28142323
Publisher site
See Article on Publisher Site

Abstract

Protective immune responses to viral infection are initiated by innate immune sensors that survey extracellular and intracellular space for foreign nucleic acids. The existence of these sensors raises fundamental questions about self/nonself discrimination because of the abundance of self-DNA and self-RNA that occupy these same compartments. Recent advances have revealed that enzymes that metabolize or modify endogenous nucleic acids are essential for preventing inappropriate activation of the innate antiviral response. In this review, we discuss rare human diseases caused by dysregulated nucleic acid sensing, focusing primarily on intracellular sensors of nucleic acids. We summarize lessons learned from these disorders, we rationalize the existence of these diseases in the context of evolution, and we propose that this framework may also apply to a number of more common autoimmune diseases for which the underlying genetics and mechanisms are not yet fully understood.

Journal

Annual Review of ImmunologyAnnual Reviews

Published: Apr 26, 2017

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