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Mitochondrial double-stranded RNAs as a pivotal mediator in the pathogenesis of Sjӧgrens syndrome
DC Field | Value | Language |
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dc.contributor.author | Yoon, Jimin | - |
dc.contributor.author | Lee, Minseok | - |
dc.contributor.author | Ali, Ahsan Ausaf | - |
dc.contributor.author | Oh, Ye Rim | - |
dc.contributor.author | Choi, Yong Seok | - |
dc.contributor.author | Kim, Sujin | - |
dc.contributor.author | Lee, Namseok | - |
dc.contributor.author | Jang, Se Gwang | - |
dc.contributor.author | Park, Seonghyeon | - |
dc.contributor.author | Chung, Jin-Haeng | - |
dc.contributor.author | Kwok, Seung-Ki | - |
dc.contributor.author | Hyon, Joon Young | - |
dc.contributor.author | Cha, Seunghee | - |
dc.contributor.author | Lee, Yun Jong | - |
dc.contributor.author | Im, Sung Gap | - |
dc.contributor.author | Kim, Yoosik | - |
dc.date.accessioned | 2023-01-02T08:02:27Z | - |
dc.date.available | 2023-01-02T08:02:27Z | - |
dc.date.created | 2022-11-01 | - |
dc.date.issued | 2022-12 | - |
dc.identifier.citation | Molecular Therapy - Nucleic Acids, Vol.30, pp.257-269 | - |
dc.identifier.issn | 2162-2531 | - |
dc.identifier.uri | https://hdl.handle.net/10371/188789 | - |
dc.description.abstract | Sjogren's syndrome (SS) is a systemic autoimmune disease that targets the exocrine glands, resulting in impaired saliva and tear secretion. To date, type I interferons (I-IFNs) are increas-ingly recognized as pivotal mediators in SS, but their endoge-nous drivers have not been elucidated. Here, we investigate the role of mitochondrial double-stranded RNAs (mt-dsRNAs) in regulating I-IFNs and other glandular phenotypes of SS. We find that mt-dsRNAs are elevated in the saliva and tears of SS patients (n = 73 for saliva and n = 16 for tears) and in salivary glands of non-obese diabetic mice with salivary dysfunction. Using the in-house-developed 3D culture of immortalized hu-man salivary gland cells, we show that stimulation by exoge-nous dsRNAs increase mt-dsRNAs, activate the innate immune system, trigger I-IFNs, and promote glandular phenotypes. These responses are mediated via the Janus kinase 1 (JAK1)/ signal transducer and activator of transcription (STAT) pathway. Indeed, a small chemical inhibitor of JAK1 attenuates mtRNA elevation and immune activation. We further show that muscarinic receptor ligand acetylcholine ameliorates auto -immune characteristics by preventing mt-dsRNA-mediated immune activation. Last, direct suppression of mt-dsRNAs re-verses the glandular phenotypes of SS. Altogether, our study underscores the significance of mt-dsRNA upregulation in the pathogenesis of SS and suggests mt-dsRNAs as propagators of a pseudo-viral signal in the SS target tissue. | - |
dc.language | 영어 | - |
dc.publisher | Nature Publishing Group | - |
dc.title | Mitochondrial double-stranded RNAs as a pivotal mediator in the pathogenesis of Sjӧgrens syndrome | - |
dc.type | Article | - |
dc.identifier.doi | 10.1016/j.omtn.2022.09.020 | - |
dc.citation.journaltitle | Molecular Therapy - Nucleic Acids | - |
dc.identifier.wosid | 000869407400004 | - |
dc.identifier.scopusid | 2-s2.0-85139732253 | - |
dc.citation.endpage | 269 | - |
dc.citation.startpage | 257 | - |
dc.citation.volume | 30 | - |
dc.description.isOpenAccess | Y | - |
dc.contributor.affiliatedAuthor | Chung, Jin-Haeng | - |
dc.contributor.affiliatedAuthor | Hyon, Joon Young | - |
dc.type.docType | Article | - |
dc.description.journalClass | 1 | - |
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