MiR-24-3p enhances the Treg/Th17 balance to improve cerebral ischemic injury by suppressing acetyl-CoA carboxylase 1 expression.

BACKGROUND

Targeting ACC1 (acetyl coenzyme A carboxylase 1) to restore the balance between T-helper 17 (Th17) cells and regulatory T cells (Tregs) through metabolic reprogramming has emerged as a promising strategy for reducing neuroinflammation following stroke. We examined the roles of potential miRNAs in regulating ACC1 expression in Tregs and treating ischemic stroke.

METHODS

The expression of miR-24-3p in CD4T cells of mice was confirmed. Then the protective effects of Ago-24-3p in a mouse model of prolonged occlusion of the distal middle cerebral artery (dMCAO) were examined. We analyzed the infiltration of Tregs and CD3T cells into the brain and evaluated the improvement of neurological deficits induced by Ago-24-3p using the Modified Garcia Score and foot fault testing.

RESULTS

Our investigation revealed that miR-24-3p specifically targets ACC1. Elevated levels of miR-24-3p have been demonstrated to increase the population of Tregs and enhance their proliferation and suppressive capabilities. Conversely, targeted reduction of ACC1 in CD4T cells has been shown to counteract the improved functionality of Tregs induced by miR-24-3p. In a murine model of dMCAO, administration of Ago-24-3p resulted in a substantial reduction in the size of the infarct within the ischemic brain area. This effect was accompanied by an upregulation of Tregs and a downregulation of CD3T cells in the ischemic brain region. In ACC1 conditional knockout mice, the ability of Ago-24-3p to enhance infiltrating Treg cells and diminish CD3T cells in the ischemic brain area has been negated. Furthermore, its capacity to reduce infarct volume has been reversed. Furthermore, we demonstrated that Ago-24-3p sustained improvement in post-stroke neurological deficits for up to 4 weeks after the MCAO procedure.

CONCLUSIONS

MiR-24-3p shows promise in the potential to reduce ACC1 expression, enhance the immunosuppressive activity of Tregs, and alleviate injuries caused by ischemic stroke. These discoveries imply that miR-24-3p could be a valuable therapeutic option for treating ischemic stroke.