Alteration of Mitochondrial DNA Copy Number and Increased Expression Levels of Mitochondrial Dynamics-Related Genes in Sjögren’s Syndrome

Benedittis, Giada De; Latini, Andrea; Colafrancesco, Serena; Priori, Roberta; Perricone, Carlo; Novelli, Lucia; Borgiani, Paola; Ciccacci, Cinzia

doi:10.3390/biomedicines10112699

Cited by 7 publications

(3 citation statements)

References 38 publications

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“…Mitochondria in salivary glandular epithelial cells show an abnormal structure with increased lymphocyte infiltration. A few studies have focused on the role of mitochondrial metabolites ( 21 ), such as cytochrome c ( 51 ), mtDNA ( 52 ) or ROS, in the immune microenvironment after salivary gland epithelial injury in pSS. In this study, TEM revealed mitochondrial swelling and autophagosome accumulation in scattered lymphocytes and ductal cells of the LSGs of patients with pSS, which is an important finding.…”

Section: Discussionmentioning

confidence: 99%

Mitochondria-related genes and metabolic profiles of innate and adaptive immune cells in primary Sjögren’s syndrome

Luo

et al. 2023

Front. Immunol.

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BackgroundPrimary Sjogren’s syndrome (pSS) is a prototypical systemic autoimmune disease characterised by lymphocyte infiltration and immune-complex deposition in multiple organs. The specific distribution of immune cell populations and their relationship with mitochondria remain unknown.MethodsHistological analysis was performed to assess the specific distribution of innate and adaptive immune cell populations in labial salivary gland (LSG) samples from 30 patients with pSS and 13 patients with non-pSS. The ultrastructural morphometric features of mitochondria within immune cells were observed under the transmission electron microscope (TEM). RNA sequencing was performed on LSG samples from 40 patients with pSS and 7 non-pSS patients. The Single-sample Gene Set Enrichment Analysis (ssGSEA), ESTIMATE, and CIBERSORT algorithms and Pearson correlation coefficients were used to examine the relationship between mitochondria-related genes and immune infiltration. Weighted Gene Co-expression Network Analysis (WGCNA) was used to identify the mitochondria-specific genes and the related pathways based on the immune cell types.ResultsHE staining revealed a massive infiltration of plasma cells with abundant immunoglobulin protein distributed around phenotypically normal-appearing acinar and ductal tissues of patients with pSS. Immunohistochemical analyses revealed that innate immune cells (macrophages, eosinophils and NK cells) were distributed throughout the glandular tissue. Dominant adaptive immune cell infiltration composed of B cells, CD4+T cells and CD8+ T cells or ectopic lymphoid follicle-like structures were observed in the LSGs of patients with pSS. TEM validated the swelling of mitochondria with disorganised cristae in some lymphocytes that had invaded the glandular tissue. Subsequently, bioinformatic analysis revealed that innate and adaptive immune cells were associated with different mitochondrial metabolism pathways. Mitochondrial electron transport and respiratory chain complexes in the glandular microenvironment were positively correlated with innate immune cells, whereas amino acid and nucleic acid metabolism were negatively correlated with adaptive immune cells. In addition, mitochondrial biogenesis and mitochondrial apoptosis in the glandular microenvironment were closely associated with adaptive immune cells.ConclusionInnate and adaptive immune cells have distinct distribution profiles in the salivary gland tissues of patients with pSS and are associated with different mitochondrial metabolic pathways, which may contribute to disease progression.

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Section: Discussionmentioning

confidence: 99%

Mitochondria-related genes and metabolic profiles of innate and adaptive immune cells in primary Sjögren’s syndrome

Luo

et al. 2023

Front. Immunol.

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“…It was previously demonstrated in animal model of SSc using Caveolin-1 (−/−) null mice that mitophagy was increased in the stromal cells of the dermis along with other signs characterizing changes in the skin in SSc (Castello-Cros et al, 2011). The study in patients with another autoimmune disease, Sjögren's syndrome have shown the decrease of mtDNA copy number and the increase of the expression of genes associated with mitochondrial dynamics in the peripheral blood of patients with Sjögren's syndrome in comparison with healthy subjects (De Benedittis et al, 2022).…”

Section: Discussionmentioning

confidence: 99%

Mitochondrial DNA copy number in patients with systemic sclerosis

Bogatyreva,

Gerasimova,

Kirichenko

et al. 2023

Front. Mol. Biosci.

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Introduction: Systemic scleroderma (SSc) is a chronic autoimmune disease of inflammatory origin. Mitochondrial dysfunction is considered as an important mechanism in the pathogenesis of SSc. Currently mitochondrial DNA (mtDNA) copy number is used as a surrogate marker of mitochondrial dysfunction. Previous studies demonstrate that innate immune cells are important participants in inflammatory and fibrotic processes in SSc. The aim of the study was to evaluate the number of mtDNA copies in CD14+ monocytes and whole blood of patients with SSc in comparison with healthy individuals.Methods: Absolute mtDNA copy number was measured using digital PCR. It was found that the number of mtDNA copies in CD14+ monocytes was significantly higher in patients with SSc compared to control, while the number of mtDNA copies in the whole blood did not have significant differences.Results: The correlation analysis revealed an inverse association of mtDNA copy number with disease duration and the relationship between pro-inflammatory activation of CD14+ monocytes in terms of LPS-stimulated IL-6 secretion and mtDNA copy number. At the same time, basal and LPS-stimulated secretion of IL-6 by cultured CD+ monocytes were significantly higher in SSc group in comparison with control.Discussion: The study results suggest that increase of mtDNA copy number in CD14+ monocytes is a possible mechanism to maintain the reduced function of defective mitochondria in monocytes from patients with SSc associated with the development and progression of SSc.

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“…Benedittis et al observed a significant increase in mitochondrial dynamics-related gene expression in SS patients, specifically in mitochondrial fission and fusion homeostasis, such as mitofusin-1 (MFN1), and mitochondrial transcription factor A (TFAM). Their research suggested a possible involvement of mitochondrial dysfunctions in the pathogenesis of SS [120]. Yoon et al found that mitochondrial double-stranded RNAs (mt-dsRNAs) were elevated in the saliva and tears of SS patients and in the salivary glands of diabetic mice with salivary dysfunction.…”

Section: Sjögren's Syndromementioning

confidence: 99%

Mitochondrial Dysfunction in the Pathogenesis and Treatment of Oral Inflammatory Diseases

Dong,

Wu,

Hong

2023

IJMS

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Oral inflammatory diseases (OIDs) include many common diseases such as periodontitis and pulpitis. The causes of OIDs consist microorganism, trauma, occlusal factors, autoimmune dis-eases and radiation therapy. When treated unproperly, such diseases not only affect oral health but also pose threat to people’s overall health condition. Therefore, identifying OIDs at an early stage and exploring new therapeutic strategies are important tasks for oral-related research. Mitochondria are crucial organelles for many cellular activities and disruptions of mitochondrial function not only affect cellular metabolism but also indirectly influence people’s health and life span. Mitochondrial dysfunction has been implicated in many common polygenic diseases, including cardiovascular and neurodegenerative diseases. Recently, increasing evidence suggests that mitochondrial dysfunction plays a critical role in the development and progression of OIDs and its associated systemic diseases. In this review, we elucidated the critical insights into mitochondrial dysfunction and its involvement in the inflammatory responses in OIDs. We also summarized recent research progresses on the treatment of OIDs targeting mitochondrial dysfunction and discussed the underlying mechanisms.

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Alteration of Mitochondrial DNA Copy Number and Increased Expression Levels of Mitochondrial Dynamics-Related Genes in Sjögren’s Syndrome

Cited by 7 publications

References 38 publications

Mitochondria-related genes and metabolic profiles of innate and adaptive immune cells in primary Sjögren’s syndrome

Mitochondria-related genes and metabolic profiles of innate and adaptive immune cells in primary Sjögren’s syndrome

Mitochondrial DNA copy number in patients with systemic sclerosis

Mitochondrial Dysfunction in the Pathogenesis and Treatment of Oral Inflammatory Diseases

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