Mitochondrial Dysfunction and Immune Dysregulation in Primary Sjogren&#39;s Syndrome: Implications for Therapeutic Strategies

Anastasia V. Poznyak; Nikolay A. Orekhov; Dmitry Felixovich Beloyartsev; Alexey V. Churov; 6; Tatiana Ivanovna Kovyanova; 3; Irina Alexandrovna Starodubtseva; Vasily N. Sukhorukov; Alexander N. Orekhov

doi:10.25163/angiotherapy.879764

Angiogenesis, Inflammation & Therapeutics | Online ISSN 2207-872X

REVIEWS (Open Access)

Mitochondrial Dysfunction and Immune Dysregulation in Primary Sjogren's Syndrome: Implications for Therapeutic Strategies

Anastasia V. Poznyak ¹*, Nikolay A. Orekhov ³, Dmitry Felixovich Beloyartsev ⁵, Alexey V. Churov ^3,6, Tatiana Ivanovna Kovyanova ^1,3, Irina Alexandrovna Starodubtseva ⁴, Vasily N. Sukhorukov ³, Alexander N. Orekhov ³

+ Author Affiliations

Journal of Angiotherapy 8 (7) 1-10 https://doi.org/10.25163/angiotherapy.879764

Submitted: 30 April 2024 Revised: 30 June 2024 Published: 02 July 2024

Abstract

Primary Sjogren's syndrome (SjS) is a complex autoimmune disorder characterized by dry eye syndrome, xerostomia, and systemic manifestations, significantly impacting patients' quality of life. Increasing evidence suggests that immune system dysfunction and chronic inflammation play a key role in the pathogenesis of primary SjS. Recent research has highlighted the involvement of mitochondrial dysfunction and its impact on the immune microenvironment of salivary glands in primary SjS. Mitochondria, essential for cellular homeostasis, are implicated in the production of reactive oxygen species, which have been associated with the pathogenesis of primary SjS. This review article comprehensively assesses the role of mitochondria in the immune dysregulation underlying primary SjS. It delves into the molecular and cellular mechanisms linking mitochondrial dysfunction to the pathogenesis of the disorder, discussing findings from gene expression studies, mitochondrial dynamics, and metabolic pathways in different immune cell populations in salivary glands. Notably, the exploration of mitochondrial DNA copy numbers in peripheral blood mononuclear cells of primary SjS subjects provides insights into the potential impact of oxidative stress and mitochondrial function in disease development. The article also discusses potential therapeutic implications, emphasizing the importance of preserving normal mitochondrial function as a promising intervention strategy for primary SjS. Furthermore, it highlights the need for further research using advanced genomic and functional approaches to validate and expand on these findings, with the goal of identifying novel therapeutic targets and advancing our understanding of the complex interplay between mitochondrial dysfunction and immune dysregulation in primary SjS.

Keywords: Primary Sjögren’s Syndrome, Mitochondrial Dysfunction, Immune Microenvironment, Oxidative Stress, Autoimmune Disorders

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