Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 24 1 2025 02 13 61 70 Leila Mohamed Khosroshahi Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran Mohammad Reza Zabihi Department of Immunology, School of Medicine Tehran University of Medical Sciences, Tehran, Iran AND Department of Bioinformatics, Laboratory of Complex Biological Systems and Bioinformatics (CBB), Institute of Biochemistry and Biophysics (IBB), University of Tehran, Tehran, Iran Behnia Akbari Department of Immunology, School of Medicine Tehran University of Medical Sciences, Tehran, Iran Jamshid Hadjati Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran Farshid Noorbakhsh Tehran University of Medical Sciences 2024 04 19 2024 04 30 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). https://ijaai.tums.ac.ir/index.php/ijaai/article/view/4085 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/4085/2139