Endogenous double-stranded Alu RNA elements stimulate IFN-responses in relapsing remitting multiple sclerosis. (June 2019)

• Record Type: Journal Article
• Authors: Heinrich, Maxwell J.; Purcell, Caroline A.; Pruijssers, Andrea J.; Zhao, Yang; Spurlock, Charles F.; Sriram, Subramaniam; Ogden, Kristen M.; Dermody, Terence S.; Scholz, Matthew B.; Crooke, Philip S.; Karijolich, John; Aune, Thomas M.
• Is Part Of: Journal of autoimmunity. Volume 100(2019)
• Page Start: 40
• Page End: 51
• Publication Date: 2019-06
• Subjects: Relapsing remitting multiple sclerosis -- Double stranded RNA sensor -- Interferons -- Alu retrotransposon; Autoimmunity -- Periodicals; Autoimmune diseases -- Periodicals; Autoantibodies -- Periodicals; Autoimmune Diseases -- Periodicals; Auto-immunité -- Périodiques; Maladies auto-immunes -- Périodiques; Electronic journals; 616.978005
• DOI: 10.1016/j.jaut.2019.02.003
• Languages: English
• ISSNs: 0896-8411

Abstract

Abstract: Various sensors that detect double-stranded RNA, presumably of viral origin, exist in eukaryotic cells and induce IFN-responses. Ongoing IFN-responses have also been documented in a variety of human autoimmune diseases including relapsing-remitting multiple sclerosis (RRMS) but their origins remain obscure. We find increased IFN-responses in leukocytes in relapsing-remitting multiple sclerosis at distinct stages of disease. Moreover, endogenous RNAs isolated from blood cells of these same patients recapitulate this IFN-response if transfected into naïve cells. These endogenous RNAs are double-stranded RNAs, contain Alu and Line elements and are transcribed from leukocyte transcriptional enhancers. Thus, transcribed endogenous retrotransposon elements can co-opt pattern recognition sensors to induce IFN-responses in RRMS. Highlights: Type 1 interferon responses are elevated at distinct stages of relapsing remitting multiple sclerosis. Endogenous RNAs isolated from blood cells of these same patients recapitulate this type 1 IFN response if transfected into naïve cells. These endogenous RNAs are double-‐stranded RNAs, contain Alu and Line elements and are transcribed from leukocyte transcriptional enhancers. In vitro transcribed Alu RNAs stimulate type 1 interferon responses. Endogenous Alu and Line double stranded RNAs may be the source of type 1 IFN responses in relapsing remitting multiple sclerosis and possibly other human autoimmune diseases. Abstract : One sentence summary: Endogenous double-stranded RNAs containing Alu and Line elements transcribed from transcriptional enhancers stimulate IFN-responses in relapsing remitting multiple sclerosis.