Inflammatory and interferon gene expression signatures in patients with mitochondrial disease
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ABSTRACT:
PROVIDER: PRJNA978503 | ENA |
REPOSITORIES: ENA
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Project description:People with mitochondrial disease 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 hyperresponsiveness to pathogens and neurodegeneration. We collected whole blood and isolated peripheral blood mononuclear cells from mitochondrial disease patients and healthy controls and examined transcriptional changes to identify common gene signatures of immune dysfunction in mitochondrial disease. We performed GSEA analyses and identified a positive enrichment of inflammatory and type I interferon gene sets in mitochondrial disease patients, coincident with a negative enrichment of T cell and B cell gene sets.
2023-06-05 | GSE233883 | GEO
Project description:BackgroundPeople 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.MethodsWe 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.ResultsGene 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.ConclusionsThrough 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.
| S-EPMC10199642 | biostudies-literature
Project description: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 hyperresponsiveness to pathogens and neurodegeneration. 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.
| S-EPMC10002836 | biostudies-literature
Project description:Mitochondrial dysfunction is associated with inflammatory bowel diseases (IBD). To understand how microbial-metabolic circuits contribute to intestinal tissue injury, we disrupt mitochondrial function in the intestinal epithelium by deleting heat shock protein 60 (Hsp60Δ/ΔIEC). While metabolic perturbation causes self-resolving tissue injury, regeneration is disrupted in the absence of aryl hydrocarbon receptor (Hsp60Δ/ΔIEC;AhR-/-) or IL-10 (Hsp60Δ/ΔIEC;Il10-/-) leading to IBD-like pathology. Tissue pathology is absent in the distal colon of germfree (GF) Hsp60Δ/ΔIEC mice, highlighting bacterial control of metabolic injury. Selective colonization of GF Hsp60Δ/ΔIEC mice with the synthetic community OMM12 confirms expansion of metabolically-flexible Bacteroides ssp., which generates metabolic injury in mono-colonized mice. Transcriptional profiling of metabolically-impaired epithelium identifies gene signatures, such as Ido1, Nos2, and Duox2, differentiating active from inactive tissue inflammation in 343 tissue sections from Crohn’s disease patients. In conclusion, mitochondrial perturbation of the epithelium causes microbiota-dependent tissue injury and discriminative inflammatory gene profiles with relevance for IBD.
2024-07-15 | PXD052829 | Pride
Project description:This SuperSeries is composed of the following subset Series: GSE35711: Transcriptional Signatures as a Disease-Specific and Predictive Inflammatory Biomarker for Type 1 Diabetes [CF_S1S3_5Auto_20CF_10HC] GSE35712: Transcriptional Signatures as a Disease-Specific and Predictive Inflammatory Biomarker for Type 1 Diabetes [H1N1_S5_5Pre_5D0] GSE35716: Transcriptional Signatures as a Disease-Specific and Predictive Inflammatory Biomarker for Type 1 Diabetes [Pneu_S3S24_10Pneu_4HC] GSE35725: Transcriptional Signatures as a Disease-Specific and Predictive Inflammatory Biomarker for Type 1 Diabetes [T1D_114] Refer to individual Series
2012-09-01 | E-GEOD-35713 | biostudies-arrayexpress
Project description:Mitochondrial perturbation in the intestine causes microbiota-dependent injury and gene signatures discriminative of inflammatory disease
| PRJEB76982 | ENA
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Project description:As metabolic dysfunction-associated steatotic liver disease (MASLD) frequently co_x0002_occurs in patients with chronic hepatitis B (CHB), the interplay between these two common liver conditions remains largely unexplored. A recent study suggest that MASH comorbidity can reduce intrahepatic interferon pathway activity and macrophage gene signatures in HBeAg_x0002_negative chronic HBV (ENEG) patients, potentially contributing to persistent infection and fibrosis. However, it remains unclear whether this phenomenon also occurs in MASLD with CHB patients.
2025-01-27 | GSE288077 | GEO
Project description:SPARC is a member of matricellular protein, and emerging evidence suggests that it plays a critical role in integrated metabolic and inflammatory responses. However, the mechanism how SPARC activates inflammation is still unanswered. Here we showed that excess SPARC induced sterile inflammation, and converted anti-inflammatory macrophage to pro-inflammatory macrophage. RNA-sequencing analysis revealed that SPARC elicits interferon-stimulated genes (ISGs) by transcription factor IRF7. SPARC also dampened mitochondrial respiration that induced pro-glycolytic inflammatory macrophage. Altogether, we discovered a mechanism how SPARC triggers sterile inflammatory response in anti-inflammatory macrophage, and this implicates the potential role of SPARC as a modulator of anti-inflammatory macrophages to maintain tissue homeostasis.
2022-08-12 | GSE167950 | GEO
Project description:Transcriptional profiles are increasingly used to investigate the severity, subtype and pathogenesis of disease. We now describe whole blood RNA signatures and local and systemic immune mediator levels in a large cohort of adults hospitalised with influenza from which extensive clinical and investigational data was obtained. Signatures reflecting interferon-related antiviral pathways were common up to day 4 of symptoms in cases not requiring mechanical ventilatory support; in those needing mechanical ventilation, an inflammatory, activated neutrophil and cell stress/death (‘bacterial’) pattern was seen, even early after disease onset. Identifiable bacterial co-infection was not necessary for this ‘bacterial’ signature but could enhance its development while attenuating the early ‘viral’ signature. Our findings emphasise the importance of timing and severity in the interpretation of transcriptomic profiles and soluble mediator levels, and identify specific patterns of immune activation that may enable the development of novel diagnostics and therapeutics
2018-03-03 | GSE111368 | GEO