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

Yong Wang; Yan Yang; Lijun Xie; Xiaona An; Lu Zhang

doi:10.1016/j.jneuroim.2024.578344

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

J Neuroimmunol. 2024 May 15:390:578344. doi: 10.1016/j.jneuroim.2024.578344. Epub 2024 Apr 16.

Authors

Yong Wang¹, Yan Yang², Lijun Xie², Xiaona An², Lu Zhang³

Affiliations

¹ Department of Anesthesiology, The PLA Strategic Support Force Characteristic Medical Center, No.9 Anxiang Beili, Chaoyang District, Beijing 100101, China.
² Department of Anesthesiology, Zibo Central Hospital, No.54 Gongqingtuanxi Road, Zhangdian District, Zibo 255020, China.
³ Department of Anesthesiology, Zibo Central Hospital, No.54 Gongqingtuanxi Road, Zhangdian District, Zibo 255020, China. Electronic address: zhangluwf@126.com.

PMID: 38640826
DOI: 10.1016/j.jneuroim.2024.578344

Abstract

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 CD4⁺T 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 CD3⁺T 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 CD4⁺T 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 CD3⁺T cells in the ischemic brain region. In ACC1 conditional knockout mice, the ability of Ago-24-3p to enhance infiltrating Treg cells and diminish CD3⁺T 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.

Keywords: Acetyl-CoA carboxylase 1; Ischemic stroke; MiR-24-3p; Regulatory T cell; T-helper 17 cell.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Acetyl-CoA Carboxylase
Animals
Brain Ischemia* / immunology
Infarction, Middle Cerebral Artery
Male
Mice
Mice, Inbred C57BL*
MicroRNAs* / genetics
MicroRNAs* / metabolism
T-Lymphocytes, Regulatory* / metabolism
Th17 Cells* / metabolism

Substances

MicroRNAs
ACC1 protein, mouse
Acetyl-CoA Carboxylase