Role of CD14+ monocyte-derived oxidised mitochondrial DNA in the inflammatory interferon type 1 signature in juvenile dermatomyositis
Authors' conclusion
These results describe a novel pathway where altered mitochondrial biology in JDM CD14+ monocytes lead to oxmtDNA production and stimulates ISG expression.
Study context
- Population
- Children with Juvenile dermatomyositis (JDM) and age/sex-matched child healthy controlsfunctional experiments: JDM n=82, CHC n=35
- Participants
- 10 / 11 / 4
- Comparison
- Pretreatment and on-treatment JDM vs child healthy controls
- Pretreatment JDMn = 10
- On-treatment JDMn = 11
- CHCn = 4reference
Methodological detailsage/sex-matched healthy controls, RNA-sequencing of sorted peripheral blood mononuclear cell (PBMC) subsets, in vitro PBMC culture experiments
- Age/sex-matched healthy controls
- RNA-sequencing of sorted PBMC subsets
- In vitro PBMC culture experiments
Main finding
As reported in the abstract
- Dysregulated mitochondrial-associated gene expression correlated with increased ISG expression in JDM CD14+ monocytes
- Altered mitochondrial biology, including 'megamitochondria', cellular metabolism and decreased SOD1 gene expression
- Associated with enhanced production of oxidised mitochondrial DNA (oxmtDNA)
- OxmtDNA induced ISG expression in healthy PBMC, blocked by targeting oxidative stress and intracellular nucleic acid sensing pathways
- In vitro, n-acetyl cysteine (NAC), TLR9 antagonist and to a lesser extent cGAS-inhibitor suppressed ISG expression in pretreatment JDM PBMC
Original publication
Role of CD14+ monocyte-derived oxidised mitochondrial DNA in the inflammatory interferon type 1 signature in juvenile dermatomyositis. Ann Rheum Dis. Published 23 December 2022. doi:10.
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