MicroRNA‑155‑5p affects regulatory T cell activation and immunosuppressive function by targeting BCL10 in myasthenia gravis

Abstract

The imbalance in immune homeostasis plays a crucial role in the pathogenesis of myasthenia gravis (MG). MicroRNAs (miRs) have been identified as key regulators of immune homeostasis. B-cell lymphoma/leukemia 10 (BCL10) has been implicated in the activation and suppressive function of regulatory T cells (Tregs). This study aimed to investigate the potential role of miR-155-5p in modulating the activation and function of Tregs in MG. To achieve this objective, blood samples were collected from MG patients to assess the expression levels of miR-155-5p and BCL10, as well as the proportion of circulating Tregs, in comparison to healthy controls. The correlation between miR-155-5p and BCL10 levels was evaluated in human samples. The expression levels of miR-155-5p and the numbers of circulating Tregs were also examined in an animal model of experimental autoimmune MG (EAMG). A dual-luciferase reporter assay was used to verify whether miR-155-5p can target BCL10. To determine the regulatory function of BCL10 in Tregs, CD4 + CD25 + Tregs were transfected with either small interfering-BCL10 or miR-155-5p inhibitor, and the expression levels of the anti-inflammatory cytokine IL-10 and transcription factors Foxp3, TGF-β1, CTLA4, and ICOS were measured. The results demonstrated that the expression level of miR-155-5p was significantly higher in patients with MG compared with that in healthy controls, whereas the expression level of BCL10 was significantly decreased in patients with MG. Furthermore, there was a significant negative correlation between the expression levels of miR-155-5p and BCL10.