title: Intracellular Nucleic Acid Detection in Autoimmunity.
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.
authors.affiliation: Department of Immunology, University of Washington School of Medicine, Seattle, Washington 98109; email: stetson@uw.edu.
authors.forename: John T
authors.initials: JT
authors.lastname: Crowl
authors.affiliation: Department of Immunology, University of Washington School of Medicine, Seattle, Washington 98109; email: stetson@uw.edu.
authors.forename: Elizabeth E
authors.initials: EE
authors.lastname: Gray
authors.affiliation: Department of Immunology, University of Washington School of Medicine, Seattle, Washington 98109; email: stetson@uw.edu.
authors.forename: Kathleen
authors.initials: K
authors.lastname: Pestal
authors.affiliation: Department of Immunology, University of Washington School of Medicine, Seattle, Washington 98109; email: stetson@uw.edu.
authors.forename: Hannah E
authors.initials: HE
authors.lastname: Volkman
authors.affiliation: Department of Immunology, University of Washington School of Medicine, Seattle, Washington 98109; email: stetson@uw.edu.
authors.forename: Daniel B
authors.initials: DB
authors.lastname: Stetson
mesh_terms: D000818:Animals; D020274:Autoimmune Diseases of the Nervous System / Q000276:immunology*; D015551:Autoimmunity; D006801:Humans; D007113:Immunity, Innate; D007370:Interferon Type I / Q000378:metabolism; D008180:Lupus Erythematosus, Systemic / Q000276:immunology*; D009421:Nervous System Malformations / Q000276:immunology*; D009696:Nucleic Acids / Q000276:immunology*; D051193:Toll-Like Receptors / Q000378:metabolism; D014777:Virus Diseases / Q000276:immunology*
chemical_list: D007370:Interferon Type I; D009696:Nucleic Acids; D051193:Toll-Like Receptors
keywords: Aicardi-Goutières syndrome; RIG-I-like receptors; Toll-like receptors; cGAS-STING; systemic lupus erythematosus; type I interferons