ArticleMolecular therapy. Nucleic acids2022
Mitochondrial double-stranded RNAs as a pivotal mediator in the pathogenesis of Sjӧgren's syndrome.
Article in Molecular therapy. Nucleic acids, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 39 citations in OpenAlex.
- Photobiomodulation for salivary gland dysfunction: aligning clinical expectations with etiology-dependent treatment responsiveness.Lasers in medical science · 2026Review
- Mitochondrial RNA-Type I Interferon Axis in Sjögren's Disease: Molecular Mechanisms and Translational Implications.International journal of molecular sciences · 2026Review
- Transcriptomic Evidence of Mitochondrial Double-Stranded RNA Accumulation in Brain Aging and Alzheimer's Disease.Aging cell · 2026Article
- Mitochondrial dysfunction activates ADAMTS-5 expression via mt-dsRNA-PKR-Spi-1 axis in osteoarthritic chondrocytes.iScience · 2026Article
- Unfolding Resilience: Molecular Integration of the Integrated Stress Response and Mitochondrial UPR in Skeletal Muscle Homeostasis.Muscles (Basel, Switzerland) · 2026Review
- Interferon-alpha selectively signals mitochondrial pore opening to allow mitochondrial RNA release in systemic lupus erythematosus: pathophysiological implications.Cell communication and signaling : CCS · 2026Article
- Mitochondrial double-stranded RNA drives aging-associated cognitive decline.Cell research · 2026Article
- ADAR1 regulates dsRNA formation in nuclear and mitochondrial transcripts through editing-dependent and -independent mechanisms.Cell reports · 2026Article
- Mitochondrial double-stranded RNA accumulation in brain aging and Alzheimer's disease.bioRxiv : the preprint server for biology · 2026Article
- Deciphering the multifaceted role of double-stranded RNA sensor protein kinase R: pathophysiological function beyond the antiviral response.RNA biology · 2025Review
- Toward unraveling molecular grammars for dsRNA-binding proteins: substrate recognition to binding mechanisms.BMB reports · 2025Review
- Taurine can restrict MtdsRNA mediated pyroptosis by enhancing mitophagy in nucleus pulposus cells.Cell communication and signaling : CCS · 2025Article
- Transcription, Maturation and Degradation of Mitochondrial RNA: Implications for Innate Immune Response.Biomolecules · 2025Review
- Diminished SUV3 expression and its functional implications in the IFN-enriched monocyte subset of childhood Sjögren's disease.Rheumatology (Oxford, England) · 2025Article
- SLIRP amplifies antiviral signaling via positive feedback regulation and contributes to autoimmune diseases.Cell reports · 2025Article
- Article
- Cellular dsRNA interactome captured by K1 antibody reveals the regulatory map of exogenous RNA sensing.Communications biology · 2025Article
- Impact of disease duration on systemic clinical profile in Sjogren's syndrome.Arthritis research & therapy · 2025Article
- Multi-Omics Mendelian Randomization Identifies Therapeutic Targets for Sjögren's Disease with Clinical and Bayesian Validation.Journal of inflammation research · 2025Article
- Mitochondrial RNA in Inflammation.International journal of biological sciences · 2025Review
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Authors and funding
16 authors at 5 institutions in 2 countries.
Funding
Abstract
Sjӧgren'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 increasingly recognized as pivotal mediators in SS, but their endogenous 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 human salivary gland cells, we show that stimulation by exogenous 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 autoimmune characteristics by preventing mt-dsRNA-mediated immune activation. Last, direct suppression of mt-dsRNAs reverses 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.
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