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Analyzing the Role of Circsnx5 in an Animal Model of Multiple Sclerosis Publisher Pubmed



Khosroshahi LM1 ; Zabihi MR1, 2 ; Akbari B1 ; Hadjati J1 ; Noorbakhsh F1, 3, 4
Authors
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Authors Affiliations
  1. 1. Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
  2. 2. Department of Bioinformatics, Laboratory of Complex Biological Systems and Bioinformatics (CBB), Institute of Biochemistry and Biophysics (IBB), University of Tehran, Tehran, Iran
  3. 3. Neuromuscular Research Center, Tehran University of Medical Sciences, Tehran, Iran
  4. 4. Shefa Neuroscience Research Center, Khatam Alanbia Hospital, Tehran, Iran

Source: Iranian Journal of Allergy, Asthma and Immunology Published:2025


Abstract

Circular RNAs (circRNAs) are endogenous non-coding RNA molecules that form covalently closed molecular loops. By regulating gene expression, circRNAs are known to play crucial roles in the development and progression of various diseases, including autoimmune, neoplastic, and neurological disorders. In this study, we examined the expression of circSnx5 in inflamed CNS tissue at different stages of experimental autoimmune encephalitis (EAE), an animal model for multiple sclerosis (MS), as well as in T cells that were activated and differentiated into different T helper phenotypes (Th1, Th17, Treg). EAE was induced and spinal cord tissues were isolated at different time points following disease induction. CD4+ T cells were isolated from mouse splenocytes and differentiated toward Th1, Th17, and Treg phenotypes, followed by the analysis of circSnx5 expression. Compared with control mice, enhanced expression of both circular and linear forms of Snx5 was detected in EAE lumbar spinal cords at the peak and post-peak phases of the disease. However, the ratio of the circular to linear forms (CLR) was decreased in EAE mice compared with controls. Expression of circSnx5 was highly correlated with the levels of inflammatory cytokines in the spinal cord tissue. Significant decreases were observed in circSnx5 expression levels following polyclonal activation of splenocytes. The expression of circSnx5 was also downregulated in differentiated T cells directed toward Th1, Th17, and Treg. Our findings suggest a potential role of circSnx5 in autoimmune neuroinflammation. The altered expression of circSnx5 during activation and differentiation may offer valuable insights into potential strategies for regulating inflammation in multiple sclerosis (MS). Copyright © 2025 Mohamed Khosroshahi et al.
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