Hsa_circ_0109623 regulates the progression of autoimmune liver disease through Hsa_miR_146b-3p/Sortilin 1-mediated activation of CD4+ T cells

Background: Autoimmune hepatitis (AIH) is a chronic liver disease characterized by immune-mediated liver inflammation. Despite its global prevalence, the pathogenesis of AIH remains poorly understood, and there is a lack of specific biomarkers and targeted treatments. This study aimed to investigate the role of hsa_circ_0109623, hsa-miR-146b-3p, and Sortilin 1 (SORT1) in AIH and their potential as therapeutic targets.

Methods: We collected liver tissue samples and peripheral blood mononuclear cells from patients with AIH and healthy controls and performed RT-PCR, western blotting, flow cytometry, and other molecular biology techniques to analyze the expression of hsa_circ_0109623, hsa-miR-146b-3p, and SORT1. We also used bioinformatics tools to predict the interaction between these molecules and conducted luciferase reporter assays to confirm their binding.

Results: hsa_circ_0109623 was significantly upregulated in patients with AIH and positively correlated with inflammatory activity. We also found that hsa_circ_0109623 could enhance CD4+ T-cell activation and promote the expression of proinflammatory cytokines. Conversely, hsa-miR-146b-3p was downregulated in patients with AIH and negatively correlated with the expression of hsa_circ_0109623 and SORT1. In addition, hsa-miR-146b-3p acted as a sponge for hsa_circ_0109623, inhibiting CD4+ Th1 cell polarization and cytokine production. SORT1 was also upregulated in patients with AIH and acted as a sponge for hsa-miR-146b-3p, promoting CD4+ Th1 cell polarization and cytokine expression. Furthermore, hsa_miR_146b-3p/SORT1 can regulate the STAT1/STAT4 signaling pathway mediating the progression of AIH.

Conclusions: The hsa_circ_0109623/hsa-miR-146b-3p/SORT1 axis plays a crucial role in the pathogenesis of AIH by regulating CD4+ T-cell activation and cytokine production. These molecules may serve as potential biomarkers and therapeutic targets for AIH. Further research is needed to validate these findings and explore their clinical applications.