Endogenous double-stranded Alu RNA elements stimulate IFN-responses in relapsing remitting multiple sclerosis.
Alu retrotransposon
Double stranded RNA sensor
Interferons
Relapsing remitting multiple sclerosis
Journal
Journal of autoimmunity
ISSN: 1095-9157
Titre abrégé: J Autoimmun
Pays: England
ID NLM: 8812164
Informations de publication
Date de publication:
06 2019
06 2019
Historique:
received:
28
11
2018
revised:
15
02
2019
accepted:
20
02
2019
pubmed:
4
3
2019
medline:
16
7
2020
entrez:
4
3
2019
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 30826177
pii: S0896-8411(18)30699-1
doi: 10.1016/j.jaut.2019.02.003
pmc: PMC6513682
mid: NIHMS1523001
pii:
doi:
Substances chimiques
RNA, Double-Stranded
0
Interferons
9008-11-1
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
40-51Subventions
Organisme : NIAID NIH HHS
ID : R21 AI128281
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI038296
Pays : United States
Organisme : NIAID NIH HHS
ID : R44 AI124766
Pays : United States
Organisme : NIAID NIH HHS
ID : R21 AI144193
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI044924
Pays : United States
Informations de copyright
Copyright © 2019. Published by Elsevier Ltd.
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