Academic Journal
Inflammatory and interferon gene expression signatures in patients with mitochondrial disease
| العنوان: | Inflammatory and interferon gene expression signatures in patients with mitochondrial disease |
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| المؤلفون: | Warren, Emily B., Gordon-Lipkin, Eliza M., Cheung, Foo, Chen, Jinguo, Mukherjee, Amrita, Apps, Richard, Tsang, John S., Jetmore, Jillian, Schlein, Melissa L., Kruk, Shannon, Lei, Yuanjiu, West, A. Phillip, McGuire, Peter J. |
| المساهمون: | Division of Intramural Research, National Institute of Allergy and Infectious Diseases, Division of Intramural Research, National Human Genome Research Institute, Office of the Assistant Secretary of Defense for Health Affairs, NHLBI |
| المصدر: | Journal of Translational Medicine ; volume 21, issue 1 ; ISSN 1479-5876 |
| بيانات النشر: | Springer Science and Business Media LLC |
| سنة النشر: | 2023 |
| الوصف: | Background People with mitochondrial disease (MtD) are susceptible to metabolic decompensation and neurological symptom progression in response to an infection. Increasing evidence suggests that mitochondrial dysfunction may cause chronic inflammation, which may promote hyper-responsiveness to pathogens and neurodegeneration. We sought to examine transcriptional changes between MtD patients and healthy controls to identify common gene signatures of immune dysregulation in MtD. Methods We collected whole blood from a cohort of MtD patients and healthy controls and performed RNAseq to examine transcriptomic differences. We performed GSEA analyses to compare our findings against existing studies to identify commonly dysregulated pathways. Results Gene sets involved in inflammatory signaling, including type I interferons, interleukin-1β and antiviral responses, are enriched in MtD patients compared to controls. Monocyte and dendritic cell gene clusters are also enriched in MtD patients, while T cell and B cell gene sets are negatively enriched. The enrichment of antiviral response corresponds with an independent set of MELAS patients, and two mouse models of mtDNA dysfunction. Conclusions Through the convergence of our results, we demonstrate translational evidence of systemic peripheral inflammation arising from MtD, predominantly through antiviral response gene sets. This provides key evidence linking mitochondrial dysfunction to inflammation, which may contribute to the pathogenesis of primary MtD and other chronic inflammatory disorders associated with mitochondrial dysfunction. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| DOI: | 10.1186/s12967-023-04180-w |
| DOI: | 10.1186/s12967-023-04180-w.pdf |
| DOI: | 10.1186/s12967-023-04180-w/fulltext.html |
| الاتاحة: | http://dx.doi.org/10.1186/s12967-023-04180-w https://link.springer.com/content/pdf/10.1186/s12967-023-04180-w.pdf https://link.springer.com/article/10.1186/s12967-023-04180-w/fulltext.html |
| Rights: | https://creativecommons.org/licenses/by/4.0 ; https://creativecommons.org/licenses/by/4.0 |
| رقم الانضمام: | edsbas.74257BEB |
| قاعدة البيانات: | BASE |
| DOI: | 10.1186/s12967-023-04180-w |
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