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

Heinrich MJ, Purcell CA, Pruijssers AJ, Zhao Y, Spurlock CF, Sriram S, Ogden KM, Dermody TS, Scholz MB, Crooke PS, Karijolich J, Aune TM
J Autoimmun. 2019 100: 40-51

PMID: 30826177 · PMCID: PMC6513682 · DOI:10.1016/j.jaut.2019.02.003

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.

Copyright © 2019. Published by Elsevier Ltd.

MeSH Terms (11)

Adult Aged Alu Elements Female Humans Interferons Long Interspersed Nucleotide Elements Male Middle Aged Multiple Sclerosis RNA, Double-Stranded

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