A Link Between Mitochondrial Dysfunction and the Immune Microenvironment of Salivary Glands in Primary Sjogren’s Syndrome

Li, Ning; Li, Yusi; Hu, Jiawei; Wu, Yi‐Cheng; Yang, Jie; Fan, Huiling; Li, Lei; Luo, Danyang; Ye, Yulin; Gao, Youhe; Xu, Hui; Hai, Wangxi; Jiang, Liting

doi:10.3389/fimmu.2022.845209

Cited by 36 publications

(33 citation statements)

References 53 publications

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“…However, in contrast with our results, a recent study reported that MFF and MFN1 are downregulated in labial salivary gland samples of Chinese SS patients stratified in different stage groups [ 34 ]. These conflicting results could be due to the different tissue investigated in the Chinese study and the particular severe phenotype analyzed.…”

Section: Discussioncontrasting

confidence: 99%

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

et al. 2022

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Sjögren’s syndrome (SS) is a chronic autoimmune multifactorial disease characterized by inflammation and lymphocytic infiltration of the exocrine glands. Several studies have highlighted the involvement of oxidative stress in this pathology, suggesting that it could induce mitochondrial dysfunctions. Mitochondria could have a role in inflammatory and immune processes. Since the mitochondrial DNA (mtDNA) copy number could change in response to physiological or environmental stimuli, this study aimed to evaluate possible alterations in the mtDNA copy number in SS. We have analyzed the amount of mtDNA in the peripheral blood of 74 SS patients and 61 healthy controls by qPCR. Then, since mitochondrial fusion and fission play a crucial role in maintaining the number of mitochondria, we investigated the expression variability of the genes most commonly involved in mitochondrial dynamics in a subgroup of SS patients and healthy controls. Interestingly, we observed a highly significant decrease in mtDNA copies in the SS patients compared to healthy controls (P = 1.44 × 10−12). Expression levels of mitochondrial fission factor (MFF), mitofusin-1 (MFN1), and mitochondrial transcription factor A (TFAM) genes were analyzed, showing a statistically significant increase in the expression of MFF (P = 0.003) and TFAM (P = 0.022) in the SS patients compared to healthy controls. These results give further insight into the possible involvement of mitochondrial dysfunctions in SS disease.

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Section: Discussioncontrasting

confidence: 99%

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

et al. 2022

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“…CMPK2 (Cytidine/uridine monophosphate kinase 2) is a thymidylate kinase, known to be associated with mitochondrial DNA (mtDNA) synthesis, and may attenuate the severity of acute respiratory distress syndrome (ARDS), a common complication of severe COVID-19, by rate-limiting for mtDNA synthesis ( 34 , 35 ). In pSS samples, CMPK2 was reported to be upregulated and was linked to the extent of immune cell infiltration, mitochondrial respiratory chain complexes, and mitochondrial metabolic pathways ( 36 ). HERC5 (HECT and RLD domain containing E3 ubiquitin protein ligase 5) is an antiviral immune protein which is induced by interferon.…”

Section: Discussionmentioning

confidence: 99%

“…mitochondrial metabolic pathways (36). HERC5 (HECT and RLD domain containing E3 ubiquitin protein ligase 5) is an antiviral immune protein which is induced by interferon.…”

Section: B Amentioning

confidence: 99%

Bioinformatics analysis of potential common pathogenic mechanisms for COVID-19 infection and primary Sjogren’s syndrome

Luo

Zhou

2022

Front. Immunol.

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BackgroundAccumulating evidence has revealed that the prevalence of Coronavirus 2019 (COVID-19) was significantly higher in patients with primary Sjogren’s syndrome (pSS) compared to the general population. However, the mechanism remains incompletely elucidated. This study aimed to further investigate the molecular mechanisms underlying the development of this complication.MethodsThe gene expression profiles of COVID-19 (GSE157103) and pSS (GSE40611) were downloaded from the Gene Expression Omnibus (GEO) database. After identifying the common differentially expressed genes (DEGs) for pSS and COVID-19, functional annotation, protein-protein interaction (PPI) network, module construction and hub gene identification were performed. Finally, we constructed transcription factor (TF)-gene regulatory network and TF-miRNA regulatory network for hub genes.ResultsA total of 40 common DEGs were selected for subsequent analyses. Functional analyses showed that cellular components and metabolic pathways collectively participated in the development and progression of pSS and COVID-19. Finally, 12 significant hub genes were identified using the cytoHubba plugin, including CMPK2, TYMS, RRM2, HERC5, IFI44L, IFI44, IFIT2, IFIT1, IFIT3, MX1, CDCA2 and TOP2A, which had preferable values as diagnostic markers for COVID-19 and pSS.ConclusionsOur study reveals common pathogenesis of pSS and COVID-19. These common pathways and pivotal genes may provide new ideas for further mechanistic studies.

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“…Damaged mitochondria produced more reactive oxygen species than healthy mitochondria, and the presence of mitochondria in pSS salivary gland cells resulted in severe ultrastructural changes ( 115 ). Recent scientific studies have shown that mitochondria-related differentially expressed genes (CD38, CMPK2, TBC1D9, and PYCR1) are closely related to the immune cell infiltration of salivary glands in pSS patients through real-time quantitative PCR ( 116 ).…”

Section: Regulation Of the Immune Microenvironmentmentioning

confidence: 99%

Composition and regulation of the immune microenvironment of salivary gland in Sjögren’s syndrome

Tan

Wang

2022

Front. Immunol.

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Primary Sjögren’s syndrome (pSS) is a systemic autoimmune disease characterized by exocrine gland dysfunction and inflammation. Patients often have dry mouth and dry eye symptoms, which seriously affect their lives. Improving dry mouth and eye symptoms has become a common demand from patients. For this reason, researchers have conducted many studies on external secretory glands. In this paper, we summarize recent studies on the salivary glands of pSS patients from the perspective of the immune microenvironment. These studies showed that hypoxia, senescence, and chronic inflammation are the essential characteristics of the salivary gland immune microenvironment. In the SG of pSS, genes related to lymphocyte chemotaxis, antigen presentation, and lymphocyte activation are upregulated. Interferon (IFN)-related genes, DNA methylation, sRNA downregulation, and mitochondrial-related differentially expressed genes are also involved in forming the immune microenvironment of pSS, while multiple signaling pathways are involved in regulation. We further elucidated the regulation of the salivary gland immune microenvironment in pSS and relevant, targeted treatments.

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A Link Between Mitochondrial Dysfunction and the Immune Microenvironment of Salivary Glands in Primary Sjogren’s Syndrome

Cited by 36 publications

References 53 publications

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

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

Bioinformatics analysis of potential common pathogenic mechanisms for COVID-19 infection and primary Sjogren’s syndrome

Composition and regulation of the immune microenvironment of salivary gland in Sjögren’s syndrome

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